MXPA06002578A

MXPA06002578A - Blood glucose level control

Info

Publication number: MXPA06002578A
Application number: MXPA/A/2006/002578A
Authority: MX
Inventors: Harel Tami; Policker Shai; Khawaled Radwan; Mika Yuval; Glasberg Offer; Rossman Aharon
Original assignee: Impulse Dynamics Nv
Priority date: 2003-09-04
Filing date: 2006-03-06
Publication date: 2006-12-13

Abstract

A method of glucose level control comprising, providing at least one electrode adapted to apply an electric field to a pancreas;and applying an electric field to the pancreas using said at least one electrode such that blood glucose levels are significantly reduced and blood insulin levels are not significantly increased compared to a regular insulin response in a same person.

Description

CONTROL OF GLUCOSE LEVEL IN BLOOD FIELD OF THE INVENTION The present invention relates to the field of blood glucose level control, especially by applying electric fields to a pancreas, to control the production of insulin.

BACKGROUND OF THE INVENTION The control of insulin secretion is very important, since there are many patients living with diabetes whose pancreas is not functioning properly. In some types of diabetes, the total level of insulin is reduced below that required to maintain normal blood glucose levels. In others, the required insulin is generated, albeit only at an unacceptable delay after the increase in blood glucose levels. In others, the body is, for some reason, resistant to the effects of insulin. Although continuous monitoring (for example, avoiding dangerous increases and decreases) of the blood glucose level is desirable, this has not been achieved in some patients at present. The process of insulin secretion works as follows: blood glucose levels are coupled to the depolarization rates of beta islet cells in the pancreas. It is postulated that when there is a higher level of glucose, a higher proportion of ATP / ADP is available in the beta cell and this closes the potassium channels, causing a depolarization of the beta cell. When a beta cell is depolarized, the calcium level in the cells increases and this high level of calcium causes the conversion of pro-insulin to insulin and causes the secretion of insulin from the cell. The beta cells are arranged in islets, within a reasonable variation of blood glucose levels, in the islet a potential action is propagated. In general, the electrical activity of a beta cell in an island is in the form of sudden increases, each sudden increase comprising a large number of small action potentials. In PCT publication WO 99/03533, the disclosure thereof is incorporated herein by reference, it was suggested to reduce the production of a pancreas using an electric field without excitation. PCT publication WO 98/57701 of Medtronic, the disclosure of which is incorporated herein by reference, suggests providing an electrical stimulating pulse to an island, causing an early initiation of a sudden increase and thus increasing the frequency of sudden increases and increasing insulin secretion. The previous PCT publication from Medtronic suggests providing a stimulating pulse (eg, the previous stimulation threshold) during a sudden increase, with the sudden increase depending on this and reducing the secretion of insulin'a. This publication also suggests stimulating different parts of the pancreas in sequence, thereby allowing the unstimulated parts to rest. However, a limitation of the methods described in the Medtronic PCT publication is that increasing the rate of sudden increase may increase the level of intracellular calcium in beta cells over a prolonged period of time, without letting the level decrease. , during the intervals intra-sudden increases. This increase can cause various mechanisms of cell death that are activated and / or otherwise upset the normal balance of the beta cell, eventually killing the cells. In addition, these high levels of calcium can cause hyper-polarization of beta cells, thereby reducing insulin secretion and preventing the propagation of action potentials. To date, there is no known device for electrical pancreatic control in operation. Diabetologia (1992) 35: 1035-1041, for example, the expositions thereof are incorporated herein by reference, describe the interaction of various hormones generated by the pancreas. Insulin improves glucose utilization, thus reducing blood glucose levels. Insulin also stimulates the secretion of glucagon, which causes the liver to secrete glucose, increasing the level of glucose in the blood. Somatostatin reduces the secretion of both insulin and glucagon. This publication also describes an experiment in which sympathetic nerve stimulation caused an increase in the secretion of somatostatin. It is suggested in this function that normal glucose levels in a healthy human being can be maintained with the help of glucagon secretion.

SUMMARY OF THE INVENTION One aspect of some embodiments of the invention relates to the reduction of glucose levels while not appreciably increasing insulin levels, at least not beyond the small amounts and / or short periods of time and / or compared to a regular response in the same person. In an exemplary embodiment of the invention, an electric field is applied to a pancreas in such a way that blood glucose levels are reduced and insulin levels are not significantly increased or even reduced by these insulin levels. In an exemplary embodiment of the invention, the reduction of glucose levels prevents an increase in insulin levels. This can have a beneficial effect on the pancreas by preventing its exhaustion. In an exemplary embodiment of the invention, insulin does not increase to more than 20%, 15%, 10%, 5% or less, or even is reduced by 5%, 10% or more. A duration of the insulin increase can be limited, for example, to less than 10 minutes, less than 5 minutes or less than 1 minute. In an exemplary embodiment of the invention, while a significant increase in insulin is observed, this increase is caused by increased levels of glucose and is considerably less than an increase of another one could have been expected for the same case of glucose ingestion . For example, the accumulated insulin secretion in a case stimulated on a glucose case can be 20%, 40% 60% or it can be reduced more compared to a control case. In an exemplary embodiment of the invention, the reduction of glucose and in some embodiments, the reduction of insulin is achieved by applying an electric field to the pancreas. In some embodiments of the invention, the electric field reduces the secretion of glucagon, directly or indirectly. Alternatively or additionally, the electric field causes the release of other non-insulin factors which reduces blood glucose levels in the blood and / or glucose absorption. In the embodiments of the invention, an electric field or other control means is used to delay gastric emptying, thereby reducing the availability of glucose. In some embodiments of the invention, the glucose levels are also reduced by the application of a stimulation to the same or a different part of the pancreas, the stimulation causes a reduction in the glucose levels via the secretion of insulin. One aspect of some embodiments of the invention relates to electrical stimulation or otherwise applying a field to a pancreas, with electrodes located away from the pancreas. In an exemplary embodiment of the invention, the electrodes are placed close to the pancreas in such a way that an electric field applied by the electrodes has a significant value in or about the pancreas. Optionally, the electric field is applied using electrodes on opposite sides of the stomach, such that a main conductive path between the electrode, which can not pass through the stomach cavity, eludes the stomach and passes through a portion of the stomach. pancreas. Optionally, the electric field has little or no effect on other organs, such as for example the stomach. Optionally, the electric field has a beneficial effect (for example, the reduction of glucose) on one or more nearby organs. A potential advantage of placing electrodes on the stomach is that the stomach is relatively stable and relatively immune to injury. In particular, the problem of a perforation or pancreatic infection can be avoided. One aspect of some embodiments of the invention relates to the timing of a glucose control therapy to prevent or reduce an initial increase in blood glucose levels in the diet. In an exemplary embodiment of the invention, therapy, for example, the application of an electric field to the pancreas, is synchronized to reduce glucagon levels quickly so that the food in digestion will not cause a large increase in glucose. Alternatively or additionally, the pancreas is controlled to provide a resistant bolus of insulin. Alternatively or additionally, the delay of gastric emptying, for example by electrical or pharmaceutical control, reduces and / or retards a high glucose level. It is believed that for some patients adequate reduction or delay of this maximum will reduce the maximum production of insulin and possibly avoid overmodulation by the pancreas. Eating can be detected, for example, automatically, for example by means of a gastric activity detector. Optionally, a pharmaceutical pump provides pharmaceutical products, for example for a slow gastric emptying. Alternatively, eating can be indicated manually, for example, by using an optical "detector" of magnetic programming. In an exemplary embodiment of the invention, a maximum of glucose due to feeding is delayed by at least 5, 10, 15 or 20 minutes. Alternatively or additionally, this maximum has its reduced amplitude (relative to an initial value) by at least 10%, 20%, 30%, 50%, 60% or more. Alternatively or additionally, this maximum has its duration shortened (duration where its value is greater than 40% over the initial value) by at least 10%, 20%, 30%, 50%, 60% or more. Alternatively or additionally, an integral on the increased levels of glucose due to feeding is reduced by at least 10%, 20%, 30%, 50%, 60% or more.

In an exemplary embodiment of the invention, a maximum of insulin due to feeding is delayed by at least 5, 10, 15 or 20 minutes. Alternatively or additionally, this maximum has its reduced amplitude (relative to an initial value) by at least 10%, 20%, 30%, 50%, 60% or more. Alternatively or additionally, this maximum has its duration shortened (duration where its value is greater than 40% with respect to the initial value) by at least 10%, 20%, 30%, 50%, 60% or more. Alternatively or additionally, an integral on the increased levels of insulin due to feeding is reduced by at least 10%, 20%, 30%, 50%, 60% or more. In an exemplary embodiment of the invention, these differences are measured with respect to a time period corresponding to the body response to a glucose case ingestion, for example, approximately 60 minutes. In an exemplary embodiment of the invention, these reductions or lack of significant increase are related to an expected increase if no control was exercised (eg, after feeding). In some modalities and / or cases, the lack of increase is related to a baseline condition. Alternatively or additionally, blood insulin values are maintained at a relatively low value, for example, less than 30, 20, 15 or 10 micro-units or ml. An aspect of some embodiments of the invention relates to a method for glucose control by electrically stimulating a pancreas with a predefined safety effect. In an exemplary embodiment of the invention, the applied field does not substantially reduce glucose levels once the initial glucose levels are reached. Alternatively or additionally, the application of the field for significant periods of time, such as, for example, several days or weeks does not cause a significant interference with the exocrine function of the pancreas and / or with the viability of the pancreas. In an exemplary embodiment of the invention, the reduction of the glucose level below the initial values is less than 30%, 20%, 10% or less. In an exemplary embodiment of the invention, glucose levels at which an additional substantial reduction is not provided are less than 40%, 30%, 20% or less during an initial glucose level. An aspect of some embodiments of the invention relates to the selective and / or integral control of various hormones generated by the pancreas and affecting the level of blood glucose, to provide control of blood glucose levels. The control can be achieved using pure electrical stimulation, or possibly using one or more pharmaceutical molecules and / or others to interact with the electrical stimulation in a desired manner. Pharmaceutical products can prevent pancreatic cells from producing and / or secreting a hormone. Alternatively, pharmaceutical products can prevent the action of the hormone, for example by blocking the receptors or deactivating the hormone. Alternatively or additionally, hormones, such as for example, insulin, somatostatin or glucagon, can be provided from outside the body or use an insulin pump. In some embodiments of the invention, the control is not exciter (defined below). In other embodiments of the invention, the control is exciter or a combination of exciter and non-exciter control. In some exemplary embodiments of the invention, the control is not simply of the blood glucose levels but also of the hormone levels required to provide a satisfactory physiological effect, rather than a simple prevention of symptomatic effects of glucose levels in the blood. wrong blood. This control can be carried out, for example, by reaching suitable short-term alternative effects or additionally by achieving convenient long-term effects. This type of two-parameter positive control is must distinguish from simple blood glucose control by varying the level of insulin. This simple control may not allow both the desired levels of blood glucose and the levels of insulin that will be reached, possibly leading to an over-exertion of the pancreas. It is conjectured that a possible reason for the lack of success of some direct or nervous stimulation of the prior art of the pancreas for glucose control is the effect of simultaneous and non-selective stimulation on the secretion of various different hormones., reducing the effectiveness of secreted hormones and / or excessive work of the pancreas. In an exemplary embodiment of the invention, the secretion of a hormone neutralizing type (eg, glucagon or insulin) is suppressed, to avoid feedback interactions where the secretion of a designated hormone (eg, insulin or glucagon) increases the secretion of the neutralizing hormone. Alternatively or additionally, the stimulation of the secretion of the designated hormone is maintained at such low levels that it does not cause a significant secretion of the neutralizing hormone. The secretion time can be extended, such that the total amount of the hormone is sufficient for a desired result. Alternatively or additionally, the stimulation of the secretion of the hormone target is controlled so that it is performed in sudden increments that are not so great to stimulate a significant secretion of the neutralizing last. Alternatively, the secretion may be sustained, to purposely cause the secretion and / or production of the neutralizing hormone to a desired degree. Alternatively or additionally, the secretion of the designated hormone is maintained at such a high level that it overcomes the neutralizing effects. Alternatively or additionally, stimulation of the secretion of the designated hormone is maintained at such a high level that it causes the generation of significant amounts of a hormone that limits secretion (eg, somatostatin), the secretion prevents the secretion of the neutralizing hormone , although not enough to prevent stimulation of the release of the designated hormone. - Alternatively or additionally, the secretion of various pancreatic hormones is suppressed by hyper-polarization of the pancreas. This hyper-polarization can be electrical by nature or chemical. For example, diazoxide causes hyper-polarization and reduces activity in the pancreas.

Alternatively or additionally, the response to beta cells (eg, insulin secretion) is moderated at high blood glucose levels, instead of being blocked, in order to avoid hypoglycemia. Alternatively or additionally, glucagon secretion is provided to prevent hyperglycemia, when high levels of insulin persist despite reduced glucose ingestion. In some cases, moderation of the insulin response and / or the provision of glucagon are used to avoid over-modulations caused, for example, by a delayed response to artificial control of the pancreas. In some cases, the insulin (or other hormone) is applied by increasing or decreasing the pulse and / or being eliminated gradually (for example, with respect to the effect or temporary frequency), to avoid this over-modulation. Alternatively or additionally, an active measurement is used, such as, for example, providing an antagonistic hormone. In an exemplary embodiment of the invention, when stimulation is used to carry out a large insulin secretion, glucose levels also increase to avoid hypoglycemia. In one example, this is provided by a glucose pump. In another, modality, this is provided by directly stimulating the glucagon libration. In another example, the secretion of insulin is greater or so rapid that directly or indirectly causes the secretion of glucagon. In one example, insulin is rapidly secreted in such a way that it can be cleared away from the bloodstream (eg, naturally or artificially reduced), causing a very high local insulin level (for the pancreas), which can stimulate the production of insulin. glucagon. Alternatively or additionally, the insulin level is carried out so high (and / or increases quite rapidly), in the body in general, to stimulate the production of glucagon. In an alternative embodiment of the invention, the insulin increase is kept low, to avoid the secretion of glucose and / or various hormones by the body, for example, by stimulating the adaptation of the relevant physiological mechanism and / or preventing the activation of the velocity sensitive mechanisms. One aspect of some embodiments of the invention is related to carrying out the control of blood levels of insulin and / or glucose by controlling the secretion of glucagon. In an exemplary embodiment of the invention, this increased glucagon secretion is used to increase blood glucose levels, rather than the reduction of or additional insulin secretion thereto. Optionally, glucagon secretion is limited to cause complete depletion of glucose sources in the liver. Alternatively or additionally, insulin secretion is stimulated by an increase in glucagon secretion. In an exemplary embodiment of the invention, both a desired glucose level and a desired insulin level can be achieved simultaneously by properly controlling glucagon secretion. Alternatively or additionally, it avoids the need for abnormally high levels by not stimulating the secretion of glucagon. In some cases, insulin secretion is provided to cause the creation of glucose stores in the liver or glucagon is provided to deplete these stores. In some exemplary embodiments of the invention, control of both glucose levels and insulin levels allows control with respect to insulin effects other than the blood glucose level, eg, the effects of lipid metabolism, gluconeogenesis in the liver, ketogenesis, storage of fats, formation of glycogen. Alternatively or additionally, the liver may be overwhelmed with glucose and / or insulin, without associated hyperglycemia, to force complete filling of glycogen stores and / or to prevent hepatic glucose uptake at a later time.

Alternative or additionally, insulin levels can be reduced in such a way that less glycogen is stored in the liver. This may be useful in von Gierke over-storage disorder and / or in other over-storage disorders. One aspect of some embodiments of the invention relates to the mapping of the response and / or feedback behavior of a pancreas. This mapping can be used, for example, for a particular patient and / or for a type of patient and / or pancreatic disorder. In an exemplary embodiment of the invention, one or more of the following properties of a pancreas are determined: (a) the interaction between two or more hormones, including one or more of the amplification gain (positive or negative), the effect of sustained short to long changes in one hormonal level or another, the delay times for the effect of one hormone on another, and / or the natural sequences of hormonal activation; (b) response to the secretion and / or production of hormones for various stimulatory and inhibitory effects, such as, for example, electric fields, pharmaceuticals and / or nerve stimulation; (c) the effect of glucose levels, pre-stimulation of the pancreas and / or pharmaceutical levels on hormonal interactions and responses to stimulation and levels of other pancreatic hormones and / or other physiological parameters, for example, levels of digestive enzymes; (d) sudden increase capacity against hormone building capacity, including, for example, the capacity and / or time constants of intracellular hormones and pre-hormonal storage; (e) different behavior of different parts of the pancreas; and (f) electrical activity of all or some of the pancreas. In some modalities, the mapping also determines the effect of non-pancreatic hormones, for example, the pituitary, thyroid and adrenal hormones. Some of these hormones can increase or decrease the blood glucose level by directly affecting the liver. In an exemplary embodiment of the invention, a direct measurement of absolute or relative hormone levels and / or a measurement of glucose levels and / or other physiological parameters, are used to determine the effect of various stimulations. These measurements can be online or offline. In an exemplary embodiment of the invention, a chemical fiber optic detector is used to analyze the hormonal levels. Alternatively or additionally, a test based on anti-body is used. In an exemplary embodiment of the invention, the controller includes a port or guidewire to the pancreatic and / or portal circulatory system. Possibly, the port or guidewire leaves the body, reaches just below the skin and / or opens into a body lumen, for easy access. This port or guidewire can be adapted to guide a catheter, for the removal of blood loaded with hormones from the pancreas. The catheter and / or guidewire can be removed once the mapping step is completed. Alternatively or additionally, the port is used to guide an endoscope, for the implantation and / or repositioning of the detectors and / or electrodes. Alternatively or additionally to measure the intra-pancreatic interactions, the adaptation of the pancreas to various physiological states and / or the adaptation of the body to various pancreatic states and / or hormone levels in the blood is also measured. This measurement can be done in a laboratory. Alternatively or additionally, a patient with a mobile or implanted device is provided to measure the previous pancreatic behavior over time. In an exemplary embodiment of the invention, the above measured behaviors are used as parameters for a predictive model of pancreatic behavior. Alternatively or additionally, a new model is created from the measurements, for example, a model of the neural network type. This model is possibly used to predict the effect of a therapy and / or to select between alternative therapies. In an exemplary embodiment of the invention, this model is used to select a therapy for the reduction of glucose level that increases insulin secretion but does not increase glucagon secretion. One aspect of some exemplary embodiments of the invention relates to the control of pancreatic behavior indirectly by controlling blood flow to the pancreas, to affect the generation and secretion of hormones and / p by controlling the blood from the pancreas, to carry out hormonal spread and / or local levels of hormones in the pancreas. In an exemplary embodiment of the invention, blood flow is controlled using non-excitatory electric fields that selectively contract or relax the arteries and / or veins to, from, or within some or all of the pancreas.

One aspect of an exemplary embodiment of the invention relates to a method for increasing insulin secretion, while avoiding unacceptable calcium levels profiles. In an exemplary embodiment of the invention, an insulin production is increased by extending a duration of sudden increase, while maintaining a suitably long interval between sudden increases, thereby allowing calcium levels to decrease during the interval. Alternatively or additionally, insulin production is increased by increasing the effectiveness of the calcium influx during a sudden increase, possibly without changing the frequency of sudden increase and / or the utilization coefficient. Alternatively, in both methods, the frequency of sudden increase can be reduced and / or increase the interval, while allowing higher levels of insulin production or maintaining the same levels of production. In an exemplary embodiment of the invention, the effects of insulin secretion are provided by applying a non-excitatory pulse to at least a portion of the pancreas. In the sense in which it is used in the present, the term non-exciter is used to describe a pulse that does not generate a new action potential, although it can modify an existing or future potential. This behavior can be a result of the pulse, amplitude, frequency or pulse envelope, and in general it also depends on the synchronization of the pulse application. It is observed that a single pulse can have excitatory and non-exciting portions. For example, a forward pulse of 100 ms may cause it to have a forward effect after 20 ms and have real non-exciting effects after 40 ms. In an exemplary embodiment of the invention, when a pulse is applied in accordance with an exemplary embodiment of the invention, it increases the amplitude of sudden increase, with the effect possibly continuing for a little longer. Optionally, the pulse does not stop the sudden increase. Possibly, the sudden increase also extends. It is believed that increasing the amplitude of sudden increase can increase the generation and / or secretion of insulin. The pulse can be synchronized to local electrical activity, for example, to sudden increases or individual action potentials. Alternatively or additionally, the pulse can be synchronized to the cycle of changes in the level of insulin in the blood (typically a 12 minute cycle in healthy human beings). Alternatively, the pulse may not be synchronized to local or global pancreatic electrical activity.

Alternatively, the applied pulse may cause the synchronization of a plurality of islands in the pancreas, for example, upon initiating a sudden increase. A two part pulse can be provided, one part to synchronize and another part to provide the non-exciting activity of the pulse. Although the term "pulse" is used, it should be noted that the applied electric field may have a duration greater than an action potential or even greater than a sudden increase. One aspect of some exemplary embodiments of the invention relates to the reduction of calcium levels in islet beta cells. In an exemplary embodiment of the invention, the levels are reduced by providing an oral drug. Alternatively, the levels are reduced by increasing the interval between sudden increases. The intervals can be reduced, for example, by suppressing the sudden increases of the action potentials, for example, by using excitatory or non-exciting pulses. Alternatively, an electrophysiological drug is provided for this purpose. For example, Procainamide HCL and Quinidine sulfate are antagonists of the Na channel, Minoxidil and Pinacidil are activators of the K channel, and Amiloride HCL is a Na channel and an epithelial antagonist. Other suitable pharmaceuticals are known in the art, for example, as described in the RBI Recipient Classification Manual, and available from RBI Inc. This reduction in calcium levels can be made to reduce the receptivity of the pancreas to glucose levels in the blood. Alternatively or additionally, this reduction is used to neutralize the negative side effects of the drugs or other treatment methods and / or to reinforce a surplus of at least a portion of the pancreas. Alternatively or additionally, this reduction can be neutralized by increasing the efficacy of insulin secretion. One aspect of some exemplary embodiments of the invention relates to advancing at least a portion of the pancreas and, at a delay after advancing, applying a non-excitatory pulse. The non-excitatory pulse may be provided to improve or suppress insulin secretion or for other reasons. In an example embodiment of the invention, the advance pulse provides a synchronization in such a way that the non-exciter pulse reaches a plurality of cells practically in a same phase of its action potentials. An additional, stimulating or non-excitatory pulse can then be provided based on the expected effect of the non-excitatory pulse on the action potential. In an exemplary embodiment of the invention, the stimulation pulse that is used to affect the production of insulin is also used to cause advancement. In one example, the pulse restores electrical activity in the pancreas, possibly in a manner similar to that of a defibrillation pulse applied to the heart. Alternatively or additionally, the stimulation pulse may cause an immediate sudden increase to occur, causing subsequent pulses that will be automatically delayed in relation to that pulse. Regardless of the actual reason for this synchronization, in an exemplary embodiment of the invention, a stimulation pulse is used that proved a short delay of a few seconds after the pulse before a new one is generated, (at least nominally) a sudden increase in normal prolongation. One aspect of some exemplary embodiments of the invention relates to simultaneously providing pharmaceutical products and electrical control of a pancreas. In an exemplary embodiment of the invention, electrical control neutralizes the negative effects of pharmaceutical products. Alternatively or additionally, the pharmaceutical product neutralizes the negative effects of the electrical control. Alternatively or additionally, the electrical control and the pharmaceutical supplement with each other, for example, the pharmaceutical product that affects the mechanisms of insulin production and electrical control that affect the mechanism of insulin secretion. The electrical control and / or pharmaceutical control can be used to control various facets of endocrine pancreatic activity, including one or more of: glucose level sensitization, insulin production, insulin secretion, cell regeneration, healing and preparation mechanisms and / or the propagation of the action potential. In an exemplary embodiment of the invention, electrical and / or pharmaceutical mechanisms are used to replace or support pancreatic mechanisms that do not work well, for example, to replace feedback mechanisms that deactivate insulin production when a level is reached. of desired blood glucose. Pharmaceutical products that act with the pancreatic controller can be provided to affect the pancreas. Alternatively, they can be provided to other portions of the body, for example to the nervous system or the cardiovascular system. One aspect of some exemplary embodiments of the invention relates to the activation of pancreatic cells in various activation profiles, for example, to achieve optimal preparation, regeneration, healing and / or utilization. In an exemplary embodiment of the invention, this activation may include one or more excitatory pulses, non-excitatory pulses and the application of pharmaceuticals and / or glucose. It is expected that diseased cells can not compete with normal loads and will degenerate if these charges are applied. However, by providing sub-normal loads, these cells can continue to function and possibly heal later while using the self-healing mechanisms. In particular, it is expected that certain diseased cells, when stimulated in at least a minimum level of activation, will heal, rather than degenerate. Alternatively or additionally, it is expected that by stressing the cells by a certain amount of compensation mechanisms, such as, for example, cell size increase, response speed and profile for glucose levels, cellular efficiency will operate and / or cell numbers, thereby causing an increase in insulin production capacity, insulin response time and / or other convenient pancreatic parameters. It may be necessary to determine the appropriate activation profiles on a patient-by-patient basis. Possibly, on a portion of the pancreas to test, different activation profiles, and if they work as desired, are applied to other portions of the pancreas. These and other portions of the pancreas can be suppressed during the test, to avoid excessive over-tension of the same. Alternatively, they can be maintained until what is judged will be a "safe" level of activity, for example, by electrical control or by the pharmaceutical product or insulin control. One aspect of some exemplary embodiments of the invention relates to electrically affecting and preferably controlling the generation of insulin, alternatively or additionally to affect insulin secretion. In an exemplary embodiment of the invention, the production of insulin is improved by "milking" the insulin of the beta cells in such a way that their insulin supplies are always the same. Alternatively or additionally, by sub-milking these cells (eg, prevention of secretion), the production of insulin is decreased. In some patients, opposite effects may occur; over-milking will cause a reduction in insulin production and / or sub-milking will increase insulin production. Alternatively, insulin production is suppressed by preventing a cell from secreting insulin (e.g., by preventing depolarization), thereby causing a large amount of insulin to remain in the cell, and possibly, preventing further production of insulin. These mechanisms to stop the production of insulin have been detected in pancreatic cells. In an exemplary embodiment of the invention, by causing a cell to store a large amount of insulin, a faster response time may be achieved, when large amounts of insulin are required, for example to combat hyperglycemia. The cells can then be depolarized systemically to provide their insulin stores. Possibly, a plurality of pancreatic cells (the same or different at different times) are periodically removed to serve as providers of insulin surges. Alternatively or additionally, the suppression of insulin production is used during medical procedures, to avoid hypoglycemia. Alternatively or additionally, the suppression or improvement of insulin production is used to overwork the pancreatic tumor cells, so that they die by overproduction or by over-storage of insulin. In some cases, the excessive work of the cells caused by the demand for cyclization can be used as a form of tension for weak cells, and in combination with another voltage source, to kill the cells. Alternatively or additionally, the suppression of insulin production is used to reduce the activity of an implanted pancreas or a pancreatic portion, to aid in its reception over the transplant chogue. One aspect of some exemplary embodiments of the invention relates to controlling the propagation of action potentials and / or other parameters of the action potentials in islet cells, alternatively or additionally to control the activity parameters in a sudden increase . In an exemplary embodiment of the invention, a pulse, optionally synchronized for individual action potentials in an island, is used to control the action potential, for example, to increase or decrease its plate life. Alternatively or additionally, a reduction in the frequency of the action potential towards the end of a sudden increase is neutralized, for example, by advancing the cells so that they have a desired frequency or are more excitable. In an exemplary embodiment of the invention, the propagation of the action potential, eg, enhanced or blocked, is controlled by selectively sensitizing or desensitizing the beta cells in an island, using chemical and / or electrical therapy. Improving the action potential may be useful to increase insulin production rates, especially if the mechanisms that are delivering glucose in some cells are damaged. The suppression of the propagation of the action potential is useful to avoid insulin production and / or reinforce the rest. One aspect of some exemplary embodiments of the invention relates to indirectly affecting pancreatic activity by changing pancreatic response parameters, such as, for example, the response time for increases in glucose level and the response gain for increases in the level of glucose. In this way, for example, a non-receptive pancreas can be sensitized, so that even small changes in the glucose level will cause an insulin leak. Alternatively, a weak or over-receptive pancreas can be desensitized, so that it is not required to generate (large amounts of) insulin during every small fluctuation in the blood glucose level. It should be noted that the two treatments can be applied simultaneously to different parts of a single pancreas. One aspect of some exemplary embodiments of the invention relates to the synchronization of the activities of different parts of the pancreas. This synchronization can take the form of all the different parts that will be activated together. Alternatively, synchronization involves activating a part (or allowing it to become active) while suppressing other parts of the pancreas (or allowing them to remain inactive). In an exemplary embodiment of the invention, synchronization is applied to reinforce the excess in different parts of the pancreas. Alternatively or additionally, synchronization is provided to selectively activate the rapidly responding parts of the pancreas or retard the responsive parts of the pancreas. In an exemplary embodiment of the invention, synchronization between islets or within islets is improved by providing pharmaceutical products, eg, Connexin, to reduce the separation resistance. These pharmaceuticals can be administered, for example, orally, systemically via the blood or locally, for example, via the bile duct. In an exemplary embodiment of the invention, these pharmaceutical products are provided by genetically altering the cells in the pancreas, for example, using genetic engineering methods. One aspect of some exemplary embodiments of the invention relates to implanting electrodes (and / or detectors) in the pancreas. In an exemplary embodiment of the invention, the electrodes are provided via the bile duct. Possibly, a controller is also provided, attached to the electrode via the bile duct. In an exemplary embodiment of the invention, the implantation procedure does not require general anesthesia and is applied using an endoscope. Alternatively, the electrodes are provided through the intestines. Possibly, the device that controls electrification of the electrodes is also provided through the intestines. In an exemplary embodiment of the invention, the device remains in the intestines, possibly in a folded outer portion of the intestines. While the electrodes protrude through the intestines and into the vicinity of the body of the pancreas. Alternatively, the electrodes can be provided through blood vessels, for example, the portal vein. In an exemplary embodiment of the invention, the electrodes are elongated electrodes with a plurality of independent or dependent contact points along the electrodes. The electrodes can be straight or curved. In an exemplary embodiment of the invention, the electrodes protrude into the pancreas in a curved manner, for example, they are guided by the endoscope, such that the electrodes cover a desired surface or volume of the pancreas. The exact coverage can be determined by imaging, or by detecting the electric field emitted by the electrodes, during a subsequent implantation calibration step. One aspect of some exemplary embodiments of the invention relates to a pancreatic controller adapted to perform one or more of the above methods. In an exemplary embodiment of the invention, the controller is implanted within the body. An example controller includes one or more electrodes, a power source for electrifying the electrodes and a control circuitry for controlling electrification. Optionally, a glucose or other type of detector is provided for feedback control. Thus, according to an exemplary embodiment of the invention, a pancreatic controller is provided, comprising: a glucose detector, for detecting a glucose or insulin level in a body serum; at least one electrode, for electrifying a cell or a group of insulin-producing cells; a source of energy to electrify at least one electrode with a pulse that does not initiate an action potential in the cell and that has an effect to increase insulin secretion; and a controller that receives the detected level and controls the energy source to electrify at least one electrode so that it has a desired effect on the level. Optionally, the insulin producing cell is contiguous with a pancreas and wherein the electrode is adapted to be placed adjacent to the pancreas. Alternatively or additionally, the controller comprises a coating suitable for long-term implantation within the body. Alternatively or additionally, the electrode is adapted to be in long-term contact with the bile fluids. Alternatively or additionally, the apparatus comprises an electrical activity detector for detecting the electrical activity of the cells and wherein the energy source electrifies the electrode at a frequency higher than that of a detected depolarization frequency of the cell, thereby causing the cell depolarizes at a higher frequency. In an exemplary embodiment of the invention, the pulse is designed to prolong a plate life of an action potential of the cell, thereby allowing more calcium influx into the cell. Optionally, the pulse is designed to reduce a frequency of the action potential of the cell, while not reducing the secretion of insulin from the cell.

In an exemplary embodiment of the invention, the pulse is designed to prolong a duration of a sudden increase activity of the cell. In an exemplary embodiment of the invention, the pulse has a sufficient amplitude to group insulin secreting cells not participating in the group of cells. In an exemplary embodiment of the invention, the apparatus comprises at least one second adjacent electrode for electrifying a second cell of the group of insulin secreting cells, wherein the controller electrifies the second electrode with a second different pulse of the first electrode. Optionally, the second pulse is designed to suppress insulin secretion. Optionally, the controller is programmed to electrify the second electrode at a later time to secrete with energy the insulin whose secretion was previously suppressed. Alternatively, the second pulse is designed to hyper-polarize the second cells. In an exemplary embodiment of the invention, the controller electrifies at least one electrode with a forward pulse having an amplitude sufficient to force a significant portion of the cells to depolarize, thereby aligning the action potentials of the cells with respect to to non-exciting pulse electrification. In an exemplary embodiment of the invention, the controller synchronizes the electrification of the electrode to a sudden increase activity of the cell. In an exemplary embodiment of the invention, the controller synchronizes the electrification of the electrode to an individual action potential of the cell. In an exemplary embodiment of the invention, the controller does not synchronize the electrification of the electrode to the electrical activity of the cell. In an exemplary embodiment of the invention, the controller does not apply the pulse to each action potential of the cell. In an exemplary embodiment of the invention, the controller does not apply the pulse to each sudden increase activity of the cell. In an exemplary embodiment of the invention, the pulse has a duration shorter than the individual action potential of the cell. Optionally, the pulse lasts less than a duration in the cell plate. In an exemplary embodiment of the invention, the pulse has a duration greater than an individual action potential of the cell. In an exemplary embodiment of the invention, the pulse has a duration greater than a duration of the sudden increase activity of the cell. In an exemplary embodiment of the invention, the controller determines electrification in response to a pharmaceutical treatment applied to the cell. Optionally, the pharmaceutical treatment comprises a pancreatic treatment. Alternatively or additionally, the controller applies the pulse to neutralize the adverse effects of the pharmaceutical treatment. In an exemplary embodiment of the invention, the controller pulses to interact synergistically with the pharmaceutical treatment. Alternatively, the controller applies the pulse to neutralize the adverse effects of advancing the stimulation of the cell. In an exemplary embodiment of the invention, the apparatus comprises an alert generator. Optionally, the controller activates the alert generator if the glucose level is below a threshold. Alternatively or additionally, the controller activates the alert generator if the glucose level is above a threshold. Also provided in accordance with an exemplary embodiment of the invention is a method for controlling insulin secretion, comprising: providing an electrode to at least a portion of a pancreas; applying a non-excitatory pulse to at least a portion of a pancreas, the pulse increases insulin secretion. Optionally, the method comprises applying an exciter pulse together with the non-exciter pulse. Alternatively or additionally, the method comprises applying a non-excitatory pulse to reduce secretion together with the non-excitatory pulse. In an exemplary embodiment of the invention, the method comprises applying a plurality of pulses in a sequence designed to achieve a desired effect on at least a portion of a pancreas. Thus, according to an exemplary embodiment of the invention, a pancreatic controller is provided, comprising: at least one electrode adapted to electrify at least a portion of a pancreas; and a controller programmed to electrify the electrode in such a way as to positively control at least the effect of at least two members of a group consisting of the blood glucose level, the blood insulin level and the blood level of another pancreatic hormone. Optionally, the control comprises modifying at least two members simultaneously. Alternatively or additionally, the control comprises selectively modifying only one of at least two members, while reducing at least one provocative interaction between the two members. Alternatively or additionally, the control comprises maintaining at least one of the members within a desired physiological variation. Alternatively or additionally, at least two members comprise the glucose level and the insulin level. Optionally, control comprises modulating an effect of insulin unrelated to carbohydrate metabolism. In an exemplary embodiment of the invention, at least one of the two members comprises glucagon. Optionally, the control comprises increasing the secretion of glucagon, to neutralize an effect of the insulin. Alternatively or additionally, the control comprises increasing the secretion of glucagon, until reaching higher levels of blood glucose. Alternatively or additionally, the control comprises reducing the secretion of glucagon, when the secretion of insulin is increased. In an exemplary embodiment of the invention, at least one of the two members comprises somatostatin. Alternatively or additionally, at least one of the members comprises a glucose level. Optionally, the controller selects between therapies for alternative control, a therapy that has at least a disturbing effect on glucose levels. In an exemplary embodiment of the invention, the controller uses only electric fields to control the members. In an exemplary embodiment of the invention, the controller extracts molecules provided in the body, taking into account, the control. Optionally, the molecules are provided without controller control. Alternatively, the molecules are provided under a control of the controller. In an exemplary embodiment of the invention, the molecules suppress the secretion of at least one pancreatic hormone. Alternatively or additionally, wherein the molecules suppress the effect of at least one pancreatic hormone. Alternatively or additionally, the molecules improve the secretion of at least one pancreatic hormone. Alternatively or additionally, the molecules improve the effect of at least one pancreatic hormone. In an exemplary embodiment of the invention, controlling a member hormone comprises suppressing a secretion of an antagonistic hormone. Alternatively or additionally, controlling a member hormone comprises improving a secretion of an antagonistic hormone. In an exemplary embodiment of the invention, the controller comprises a module with learning memory for storing the pancreas feedback interaction therein. Optionally, feedback interactions include interactions between hormone levels. Alternatively or additionally, feedback interactions comprise the interactions between hormone levels. Alternatively or additionally, feedback interactions depend on blood glucose levels. Alternatively or additionally, the feedback interactions are determined by the controller, by tracking pancreas behavior. Optionally, the controller actively modifies at least one glucose level and one pancreatic hormone level, to collect the information from the feedback interaction. In an exemplary embodiment of the invention, the controller comprises a detector for detecting a level of the controlled member. Alternatively or additionally, the controller comprises an estimator for estimating a level of the controlled member. Alternatively or additionally, the electrode applies a non-excitatory pulse to carry out the control. Alternatively or additionally, the electrode applies an exciter pulse to carry out the control. In an exemplary embodiment of the invention, the electrode modifies the blood flow associated with the pancreas to carry out the control. Optionally, the modified blood flow comprises a blood flow for hormone-generating cells of the pancreas.

Alternatively, the modified blood flow comprises a blood flow from the pancreas. In an exemplary embodiment of the invention, the modified blood flow comprises a blood flow from the hormone-generating cells of the pancreas. In an exemplary embodiment of the invention, at least one electrode comprises at least two electrodes that selectively electrify different portions of the pancreas, until a desired control of at least two members is achieved. In an exemplary embodiment of the invention, controlling comprises control of secretion. In an exemplary embodiment of the invention, controlling comprises control of production.

Alternatively or additionally, controlling comprises the control of physiological activity. Also provided in accordance with an exemplary embodiment of the invention is a method for mapping the pancreatic behavior of a pancreas, comprising: determining a pancreatic behavior in a first set of conditions; determine a behavior of a pancreas in a second set of conditions; and analyze the behavior of the pancreas and the sets of conditions, to determine a pattern of behavior of the pancreas. Optionally, the pattern of behavior includes an interrelation between two hormones of the pancreas. Alternatively or additionally, the sets of conditions naturally occur. Alternatively, the sets of conditions are at least partially induced artificially. In an exemplary embodiment of the invention, the method comprises controlling the response of the pancreas to the determined behavior. Optionally, control comprises control using pharmaceutical products. Alternatively or additionally, controlling comprises control using electric fields. Also provided in accordance with an exemplary embodiment of the invention is a method for controlling the sudden increase activity of a pancreas, comprising: applying an electric field to at least a portion of a pancreas in such a way that the increase activity sudden start a few seconds after the application; and repeating the application a plurality of times in such a way that practically all of the sudden increase activity of the pancreas portion during a period of time between the applications is synchronized for the application and a repeated application. Optionally, the method comprises varying a repetition rate of the application to control a sudden rate of increase of at least a portion of a pancreas. Also provided in accordance with an exemplary embodiment of the invention is a method for controlling the activity of a pancreas, comprising: providing a source of electric fields; and electrifying the source to apply an electric field to at least a portion of a pancreas, such that the applied field increases an amplitude of at least one sudden increase after application. Optionally, the applied field does not induce a new sudden increase. Alternatively or additionally, the applied field does not substantially change a sudden rate of increase of the pancreas. Alternatively or additionally, the sudden increase in increased amplitude provides an increased level of insulin relative to a sudden increase in normal amplitude. Alternatively or additionally, the method comprises synchronizing the electrification to a natural sudden increase sequence of at least a portion of a pancreas. Also provided in accordance with an exemplary embodiment of the invention is a method for controlling the glucose level, comprising: providing at least one electrode adapted to apply an electric field to a pancreas; and applying an electric field to the pancreas using at least one electrode in such a way that the blood glucose levels are significantly reduced and the blood insulin levels are not significantly increased compared to the regular insulin response in the same person. Optionally, the method involves applying a second electric field to the pancreas later, the second electric field increases the insulin levels. Optionally, the electric field works to reduce the secretion of glucagon. Optionally, the electric field works to reduce the secretion of glucose by a liver physiologically coupled to the pancreas. Optionally, the electric field works to increase the absorption of glucose by cells in a body that contains the pancreas. Optionally, the electric field works to affect the nervous tissue in the pancreas. Optionally, the electric field is not exciter since it does not induce substantially new sudden increases in islet activity in the pancreas. Optionally, the electric field is applied as a bi-phased balanced time and load variable field. Optionally, the electric field is applied for a short duration each period of time. Optionally, the time period provides an application frequency between 1 Hz and 15 Hz. Alternatively or additionally, the time period provides an application frequency of approximately 5 Hz. Alternative or additional entity, the duration is less than 30 ms. Alternatively or additionally, the duration is approximately 10 ms. Optionally, the electric field is repeated for a period of less than 30 minutes. Optionally, the electric field is repeated for a period between 30 and 180 minutes. Optionally, the electric field is practically applied in the total duration of a case of glucose absorption. Optionally, the electric field is applied before an expected case of glucose insertion.

Optionally, the method comprises activating the electric field through a case of glucose ingestion. Optionally, the electric field is applied regardless of whether there is a case of ingestion. Optionally, the electric field is at least part of the time regardless of a blood glucose level. Optionally, the electric field is applied continuously for at least 24 hours. Optionally, the electric field is applied for a period of at least 15 minutes without sensitization of its effect. Optionally, the electric field is of a magnitude and temporal degree in such a way that it does not significantly change the levels of insulin and glucose in blood in the absence of a case of ingestion. Optionally, the electric field reduces blood glucose levels by at least 20% of a glucose level rise greater than a fasting initial value of glucose level. Optionally, the electric field does not increase blood insulin levels, as measured by an average for five minutes, not greater than 20%. Optionally, the electric field reduces the levels of insulin in blood, as measured by an accumulated amount for a case of glucose ingestion and compared to a regular response of the person, greater than 20%. Optionally, the method comprises delaying a gastric emptying by applying a treatment to the stomach. Optionally, the electric field works to retard a maximum of glucose for at least one duration of its application. Optionally, the electric field works to delay a maximum of glucose for at least 10 minutes. Optionally, the electric field works to delay a maximum of insulin for at least 10 minutes. Optionally, the electric field works to truncate a maximum of insulin. Optionally, the electric field works to truncate a maximum of glucose. Optionally, the electrode does not attach to a pancreas. Optionally, the electrode is attached to a pancreas. Also provided in accordance with an exemplary embodiment of the invention is a method for controlling the glucose level, comprising: providing at least one electrode adapted to apply an electric field to a pancreas; and applying an electric field to the pancreas that works to reduce blood glucose levels if they are elevated and does not significantly reduce these levels in an important way if they do not rise substantially. Optionally, the electric field reduces high glucose levels by at least 20%. Optionally, the electric field does not significantly reduce non-elevated glucose levels by more than 10%. Optionally, the electric field does not damage the exocrine functions of the pancreas. Also provided, according to an exemplary embodiment of the invention, is an apparatus for controlling blood glucose, comprising: at least one electrode adapted to apply an electric field to a pancreas; and circuitry adapted to electrify at least one electrode and configured to electrify the electrode with a non-exciter field so as to compensate for a significant loss of response by the pancreas. Optionally, the circuitry compensates by causing the secretion of a bolus of insulin. Optionally, the circuitry compensates by reducing glucose levels so that they are not insulin. Optionally, the circuitry compensates by reducing the glucagon secretion.

Optionally, the circuitry reduces or prevents a substantial increase in insulin secretion during compensation. Optionally, during at least 20% of the cases of ingestion the circuitry applies only an important control of insulin levels. Optionally, the apparatus is programmed with a knowledge of an insulin therapy based on slow-acting chemicals provided to the pancreas. Optionally, the apparatus comprises an automatic ingestion detector to automatically detect a case of ingestion. Optionally, the apparatus comprises an automatic glucose detector to automatically detect a situation that requires an important response. Optionally, the apparatus comprises an automatic glucose detector to automatically detect a situation that requires a significant insulin response. Optionally, the response is an important insulin response. Optionally, the electrode is adapted to be attached to a pancreas. Optionally, the electrode is adapted to join a muscular organ.

Also provided, according to an exemplary embodiment of the invention, is an apparatus for controlling blood glucose, comprising: at least one electrode adapted to apply an electric field to a pancreas; and circuitry adapted to electrify at least one electrode and configured to electrify the electrode so as to significantly reduce high blood glucose levels, the circuitry is configured to apply the field also when glucose levels are not raised. Optionally, the circuitry is a closed circuit system that includes detecting the effect of electrification and where the circuitry is configured for over stimulation in cases of doubt. Optionally, the circuitry is a semi-open circuit system where a series of relatively long stimulation is applied without back-feeding. Optionally, the circuitry is an open circuit system where a series of stimulation is applied that responds to an activation and without feedback. Also provided in accordance with an exemplary embodiment of the invention is an apparatus for controlling blood glucose, comprising: at least one electrode adapted to apply an electric field to a pancreatic tissue; and circuitry adapted to electrify an electrode and configured to electrify the electrode so as to reduce glucose levels and does not substantially raise insulin levels above an initial value, when glucose levels are raised. Optionally, the circuitry is a closed circuit system that includes the sensitization of the effect of electrification and where the circuitry is configured to be over-stimulated in cases of doubt. Optionally, the circuitry is a semi-open circuit system where a series of relatively long stimulation is applied without feedback. Optionally, the circuitry is an open circuit system where a series of stimulation is applied that responds to an activation and without feedback. Optionally, the circuitry applies a constant voltage field. Optionally, the circuitry applies a constant current field. Optionally, the pancreatic tissue comprises a pancreas xn vxvo. Optionally, the pancreatic tissue comprises a pancreatic tissue implant. Optionally, the initial value is an insulin response of initial value of a person for whom the device is used. Also provided in accordance with an exemplary embodiment of the invention is a method for controlling the level of insulin, comprising: providing at least one electrode adapted to apply an electric field to a pancreas; and applying an electric field to the pancreas using at least one electrode in such a way that blood glucose levels are not significantly increased and blood insulin levels are significantly reduced. Also provided in accordance with an exemplary embodiment of the invention is a method for applying an electrical field to a pancreas or a positionally functional and associated tissue, comprising: attaching at least one electrode to a tissue other than the pancreas; and electrifying the electrode such that a significant field is applied to the pancreas or associated tissue to control at least one of a level of a pancreatic secretion and a blood glucose level. Optionally, the method comprises using at least one electrode to also control feeding habits. Also provided in accordance with an exemplary embodiment of the invention is an apparatus for applying a field -electric * to a pancreatic or a functionally positionally associated tissue, comprising: at least one electrode adapted to be attached to a different tissue of the pancreas; and means for electrifying the electrode such that a significant field is applied to the pancreas or associated tissue to control at least one of a level of a secretion of the pancreas and a blood glucose level.

BRIEF DESCRIPTION OF THE FIGURES Particular embodiments of the invention will be described with reference to the following description of the exemplary embodiments together with the Figures, wherein identical structures, elements or parts that appear in more than one Figure are optionally labeled with an equal or similar number in all the Figures in which they appear, in which: Figure 1 is a block diagram of a pancreatic controller, according to an example embodiment of the invention; Figure 2 is a diagram of an example electrical activity of a single beta cell, operating at slightly elevated glucose levels; Figure 3A is a flow diagram of a logic scheme for example control, according to an exemplary embodiment of the invention; Figure 3B is a flow diagram of another example control logic scheme, according to an exemplary embodiment of the invention; Figures 4A-4D illustrate different types of electrodes that may be suitable for pancreatic electrification, in accordance with an exemplary embodiment of the invention; Figure 4E illustrates an electrode, in which the body of the controller of Figure 1 serves as at least one electrode, according to an exemplary embodiment of the invention; Figure 5 illustrates a pancreas subdivided into a plurality of control regions, each region being electrified by a different electrode, according to an exemplary embodiment of the invention; Figures 6A and 6B are flow charts of implantation methods, according to an exemplary embodiment of the invention; Figure 6C is a schematic illustration of an abdominal cavity showing the placement of electrodes in a stomach in proximity to a pancreas, according to an exemplary embodiment of the invention; Figure 7 is a flow diagram of an exemplary method of implementing and programming the controller, in accordance with an exemplary embodiment of the invention; Figure 8A is a diagram showing the effect of electrical stimulation on insulin levels in six animals; Figures 8B-8D are diagrams of an experiment in a pancreas in sxtu, showing an increase in insulin secretion, according to an exemplary embodiment of the invention; Figure 9 is a graph showing the effect of electrical stimulation on blood glucose levels, in an experiment in which glucose levels are increased faster than would be expected solely by inhibition of. the secretion of insulin; Figures 10A-10B are a diagram and a pulse diagram, respectively, of an experiment showing the reduction of glucose levels as a result of applying an electrical pulse according to an exemplary embodiment of the invention; Figures 11A-11B are a diagram and a pulse diagram, respectively, of an experiment showing the reduction of glucose levels as a result of applying an electrical pulse according to an exemplary embodiment of the invention; Figures 12A-12B are a diagram and a pulse diagram, respectively, of an experiment showing the reduction of glucose levels as a result of applying an electrical pulse according to an exemplary embodiment of the invention; Figures 13A-13B are a diagram and a pulse diagram, respectively, of an experiment showing the reduction of glucose levels as a result of applying an electrical pulse according to an exemplary embodiment of the invention; Figure 14 is a diagram showing an experiment in which the application of stimulation pulses increases the amplitude of the sudden increases but does not induce new sudden increases; Figures 15A-15C are a diagram and two enlargements thereof of an experiment showing that a stimulation pulse synchronizes the activity of sudden increases, possibly without immediately generating a new sudden increase; Figures 16A-16C are a diagram and two enlargements thereof of an experiment showing the induction of a new sudden increase by a stimulation pulse; Figure 17 is a diagram of an experiment showing that a stimulation in the middle of a sudden increase does not stop the sudden increase; Figures 18A and 18B are diagrams showing changes in insulin level apparently caused by stimulation; Figure 19 is a diagram showing the relative constant levels of glucose in a rat pancreas perfused without stimulation; Figure 20A is a diagram showing the changes in insulin levels with and without stimulation, in a live mini-pig that was given to eat sugar cubes; Figure 20B is a diagram corresponding to diagram 20A, showing the case of stimulation of the relationship between glucose level and insulin level; Figure 20C is a diagram corresponding to diagram 20A, showing the steps without stimulation, the relationship between the glucose and insulin level; Figure 21A is a diagram showing changes in insulin levels with and without stimulation in a live mini-pig that was fed; Figure 21B is a diagram corresponding to diagram 21A, showing the blood glucose levels; Figure 22A is a diagram showing a delay in the maximum increase in glucose and reduction of glucose levels under stimulation conditions in a series of experiments on a first pig, according to an exemplary embodiment of the invention; Figure 22B is a diagram showing a delay in maximum insulin increase and reduction in insulin levels in a series of experiments under stimulation conditions in the first pig according to an exemplary embodiment of the invention; Figure 22C is a diagram showing the reduction of glucagon as a result of the application of a stimulation according to an exemplary embodiment of the invention; Figure 23 is a diagram showing a reduction of glucose levels under stimulation conditions in a series of experiments in a second pig, according to an exemplary embodiment of the invention; Figure 24 is a diagram showing a reduction of glucose levels under stimulation conditions in a series of experiments in a third pig, according to an exemplary embodiment of the invention; Figure 25 is a diagram illustrating that a stimulation for glucose reduction according to an exemplary embodiment of the invention, works under hyperglycemic IV fixation conditions; Figure 26 is a diagram showing a lack of damaging stimulation effect according to an exemplary embodiment of the invention, on normal glucose levels; Figure 27 is a diagram showing the effect, in a human being, on glucose levels, of a stimulation according to an example embodiment of the invention; Figure 28 is a diagram showing the effect, in a human being, on insulin levels, of a stimulation according to an exemplary embodiment of the invention; Figure 29 is a diagram showing the effect, in a human being, on the levels of the C-peptide, of a stimulation according to an example embodiment of the invention; Figures 30A and 30B are diagrams showing a lack of dangerous effect of the stimulation according to an example embodiment of the invention, on the fasting human glucose levels; Figures 31A and 31B are diagrams showing a lack of dangerous stimulation effect according to an example embodiment of the invention, on the fasting human insulin levels; Figures 32A and 32B are diagrams showing a reduction of glucose and insulin in a pig, according to an exemplary embodiment of the invention; Figures 32C and 32D show cumulative levels of glucose and insulin in the pig of Figures 32A and 32B; Figures 33A and 33B are diagrams showing the reduction of glucose and insulin in another pig, according to an exemplary embodiment of the invention; Figures 33C and 33D show accumulated levels of glucose and insulin in the pig of Figures 33A and 33B; Figure 34 shows accumulated levels of glucose under various field application conditions, according to an exemplary embodiment of the invention; Figures 35A and 35B are diagrams showing the reduction of glucose and insulin in another pig, according to an exemplary embodiment of the invention; Figures 35C and 35D show accumulated levels of glucose and insulin in the pig of Figures 35A and 35B; Figure 36 shows a reduction of the glucose level in another pig, according to an exemplary embodiment of the invention; Figures 37A and 37B are diagrams showing a reduction of glucose and insulin in a dog, according to an exemplary embodiment of the invention; Figures 38A and 38B are diagrams showing a reduction of glucose in two dogs where the electrodes were placed in a stomach, according to an exemplary embodiment of the invention; Figure 38C is a diagram showing the variable effect of experiments with intermittent experiments with continuous signal application to a dog, according to the example embodiment of the invention; Figure 38D is a schematic diagram showing the relative locations of a right lobe of a pancreas and a stomach in a dog; and Figures 39A and 39B are diagrams showing the reduction of glucose in two dogs where the electrodes were placed in a stomach, according to an exemplary embodiment of the invention. i DETAILED DESCRIPTION OF THE INVENTION Figure 1 is a block diagram of a pancreatic controller 102, according to an exemplary embodiment of the invention. In an exemplary embodiment of the invention, the device 102 is used to provide electrically controlling pulses to a pancreas 100. These control pulses may include excitatory stimulating pulses and non-exciting pulses. In particular, these pulses can include pulses of advance and pulses to modify the action potential. In an exemplary embodiment of the invention, the control pulses are used to control a patient's glucose and insulin level. In addition, a particular desired profile of glucose and / or insulin can be achieved. Alternatively or additionally, the secretion and / or generation of other pancreatic hormones can be controlled. Other uses of controller 102 will be evident a. from the following description and may include, for example, preparation, healing and prevention of pancreatic cell damage. Descriptive and non-limiting examples of metabolic and / or hormonal disorders that can be treated by the proper application of the methods described below, include diabetes mellitus that is not insulin-dependent, insulin-dependent diabetes mellitus, and hyperinsulinemia. The following description includes many different pulses that can be applied until a desired effect is achieved; it should be clear that the scope of the description also covers an apparatus, such as for example the controller 102 which is programmed to apply the pulses and / or process the feedback, as required. It should be noted that a desired effect can be achieved by applying various combinations of the pulses described below, for two different sequences. Particular combinations of pulses that are suitable for a particular patient may need to be determined on a patient-by-patient basis and may change over time. The pulses and example sequences, however, are described below.

EXAMPLE DEVICE A pancreatic controller 102, generally includes a source of fields 104 for generating electric fields through the pancreas 100 or portions thereof, this field source is controlled by a control circuitry 106. An energy source 108 optionally supplies power to the field source 104 and the control circuitry 106. The electrification is applied using a plurality of electrodes, for example, a common electrode 110 and a plurality of individual electrodes 112. Alternatively other electrode schemes are used, for example , a plurality of pairs of electrodes. Electrical and other detectors can also be provided for the input of the controller 106. While the electrodes can also serve as electrical detectors, in an exemplary embodiment of the invention, the detectors are provided separately, such as, for example, a detector pancreatic 114 or a blood glucose detector 118 in a blood vessel 120. Extra-cellular detectors may also be provided to measure intercellular glucose levels. The controller 102 may also include an external unit 116, for example, for transmitting power or programming for the control circuitry 106 and / or the power source 108. Alternatively or additionally, the external unit may be used to provide indications from a patient and / or the information of the detectors. Alternatively or additionally, the external unit may be used to provide alerts to the patient, for example, if the glucose level is not under adequate control. Alternatively or additionally, these alerts can be provided from within the body, for example, by using low frequency probes or by electrical stimulation of a nerve, muscle or intestines. Additional details of this and other example implementations will be provided later. Nevertheless, the general structure of the controller 102 may use elements and design principles used for other electrophysiological controllers, for example, as described in PCT publications W097 / 25098, W098 / 10831, W098 / 10832 and the patent application of United States 09 / 260,769, granted as the patent 6,292,693, the disclosure of which is incorporated herein by reference. It should be noted, however, that the frequencies, energy levels and duration of the pulses in the pancreas may be different from those used, for example, in the heart. In particular, energy levels may be lower. Additionally, the immediate effects of an error in applying a pulse to the pancreas are not expected to threaten life as a similar error could occur in the heart, except for the possibility of tissue damage, which could cause an increase in severity of the patient's disease.

TISSUE TO WHICH THE CONTROLLER APPLIES The present invention is described primarily with reference to pancreatic tissues. This tissue may be in the pancreas or be part of an implant, possibly in any part of the body, or even in the same envelope of the controller, the implant comprises, for example, homologous, autologous or heterologous tissue. Alternatively or additionally, the implant can be genetically modified to produce insulin. It should be noted that different parts of the pancreas may have different behavior related to secretion and / or a response to electric fields.

ELECTRICAL ACTIVITY IN THE PANCREAS Figure 2 is a diagram of an example electrical activity of a single beta cell that operates at slightly elevated glucose levels. In a large scale graph 130, it is shown that the activity of an individual cell comprises a plurality of sudden increase periods 132 comprising a plurality of individual action potentials and separated by a plurality of interval periods 134, in which the periods have virtually no action potentials. As shown in an enlarged graph 140, each sudden increase comprises a plurality of depolarization events 142, each followed by a re-polarization period 144. The intra-cellular calcium level increases during the sudden increase 132 and decreases during the interval 134. The beta cells of a pancreas are arranged in islets, each islet acts as an individual activation domain, in which, when the glucose levels are very high, a propagation of the action potential will be found. In this way, the aggregate electrical activity of an island is that of an average action potential of repetition, at a frequency of, for example, 1 Hz, which in general depends on the propagation time of an action potential through the island. . During intervals 134, if too many beta cells share the interval, the total islet in general may be imperceptible or contain only sporadic depolarization periods. The individual cells can operate at higher frequencies, for example, 5-20 Hz. Alternatively or additionally, a slow wave can provide a wrap of approximately 3-5 cycles / min. It should be noted that the synchronization and / or correlation between cells in an island may depend on the junctions in the separation between the beta cells and others. The resistance of these separation connections depends on the glucose and / or hormonal levels, and as such, can also be determined and controlled, according to some embodiments of the invention. Alternatively or additionally, the level of synchronization in an island and / or between islets can be used as an indicator for glucose and / or hormonal levels. Recent studies suggest that the timing of different parts of the pancreas is supplied by nerve paths. In an exemplary embodiment of the invention, these nerve paths are stimulated and / or blocked by the application of electric fields and / or pharmaceutical products, in order to achieve desired results. An example of this study - is described in "Pulsatile insulin secretion: detection, regulation, and role in diabetes", Diabetes ... February 2002; 51 Suppl 1: S245-54, by Porksen N, Hollingdal M, Juhl C, Butler P, Veldhuis JD, Schmitz O, of the Department of Endocrinology and Metabolism M, Aarhus University Hospital, Aarhus, Denmark, the exhibition of which is incorporated herein as a reference.

INCREASE IN INSULIN SECRETION Insulin secretion, as differentiated from insulin production, can be increased in various ways, according to an exemplary embodiment of the invention. The following methods may be applied together or separately. Also, the methods can be applied locally, to select portions of the pancreas, or globally, to the pancreas as a whole. In a first method, the duration of a sudden increase 132 is increased, thereby allowing a greater amount of calcium to beta cells. It is believed that the level of calcium in the cell is directly related to the amount of insulin released by the cells. One type of pulse that can be applied is a forward pulse that forces depolarization of the cells in the island. This pulse is optionally applied to the same frequency according to the individual action potentials, for example, 10 Hz. However, advancement in each action potential may not be necessary, a periodic advance signal may be sufficient to force continuous depolarization events. As is known in the cardiac advance technique, many techniques can be applied to increase the probability of capture of the advance signal, for example, double advance, formation and pulse duration. . These methods can also be applied, with appropriate modifications, for the advancement of the pancreas. An alternative method to increase the length of sudden increases is by increasing the sensitivity of the beta cells to depolarization, for example, by pulses having a sub-threshold. Another method of sensitizing the cells and / or increasing the duration of their action potential is by hyperpolarizing the cells before a forced or normal depolarization. Possibly, in order to avoid the normal reduction of the frequency of depolarization toward the end of a sudden increase, a greater production of insulin can be achieved for the same length of sudden increase. In another method, insulin secretion is increased by increasing the efficiency of the calcium influx of individual action potentials. In an exemplary embodiment of the invention, this is achieved by increasing the length of the plate durations 144, for example by applying an electrical pulse during the repolarization period associated with each of the depolarization events 142. If a pulse well in advance in the repolarization phase of a period of action potential before closing the calcium channels that provide the influx of calcium, these channels can remain open for prolonged periods and provide greater influx of calcium. It should be noted that the frequency of activation of the beta cells can be reduced. In some cells, the influx of calcium may be more efficient during the depolarization period.

In these cells, the depolarization period 142 optionally extends, for example, by applying an additional depolarization pulse during depolarization or almost immediately thereafter. Alternatively or additionally, a pharmaceutical product may be provided which enhances depolarization, such that the repolarization time is shortened and the increase in the duration of a sudden increase 132 may be exhausted in cases of depolarization. Alternatively or additionally, the plate duration can be shortened by applying an adequate pulse during the plate stay. In one example, the application of a pulse after the calcium channels are closed is expected to shorten the repolarization time. Alternatively or additionally, the individual action potentials are advanced at a higher than normal rate for the glucose level. This advance can nullify the completion of repolarization and force more frequent depolarization events. It should be noted that a rate of advance considerably greater can be achieved by advancing rather than what could naturally occur for the same physiological conditions. Possibly, the rate of advance is greater than the physiological normal for an island at any glucose level. In another method, insulin secretion is improved by advancing the islets so that they have a higher frequency of sudden increases (as opposed to a higher frequency of action potentials, described above). The resulting shortening of the intervals 134 may have undesired effects, for example, by maintaining high levels of calcium in a cell for a very long period of time. In an exemplary embodiment of the invention, this shortening of the potential is overcome by increasing the interval durations, for example, by applying a hyper-polarizing pulse during the interval, thereby allowing calcium to exit the beta cells. It should be noted however, that in some cases, sustained high calcium levels may be desirable, in which case, the intervals may be artificially shortened. In compensation, the efficacy of the sudden increase can be reduced to cause the secretion of insulin. A potential advantage of the advance is that the signal of 'advance > it will cause depolarization and an associated cluster of beta cells that otherwise could not be carried out in the activity of the pancreas. It is expected that as intracellular calcium levels increase (or some other control mechanism), some cells will stop participating in the electrical activity. When applying a forward pulse, it is expected that these cells will be forced to participate and, in this way, "continue to secrete insulin." Another potential advantage of the advance is related to the synchronization problem, as it can be seen, some types of pulses Controllers should be applied at a certain stage in the cell action potential In a situation of propagation action potential, it may be difficult to provide an individual pulse with a timing that matches all cells, especially as the frequency increases However, by forcing the simultaneous depolarization of a total islet, the phases are synchronized, making it possible to more easily reach a suitable pulse timing, however, it should be noted that even if there is no advance, some pulses , such as, for example, for the extension of the plate permanence of one of the action potentials, can be applied at a time that is effective for a larger fraction of cells in the island. In some exemplary methods of increasing insulin secretion, the amplitude of island depolarization increases. evidently. This can be, for example, by grouping cells that are not otherwise involved, or they can be the result of cell synchronization in such a way that the electrical signals are additive.

Alternatively or additionally to the transport of vesicle supplied by calcium, in an exemplary embodiment of the invention, the electric field may also directly release insulin from the REP or the cell and / or from other organelles in the cell.

SUPPRESSION OF INSULIN SECRETION In some cases, for example if the glucose level is very low, it may be convenient to suppress insulin secretion. Again, the following methods can be applied together or separately. Also, as noted above, different methods can be applied to different parts of the pancreas, for example, by electrodes with different electrification 112 of Figure 1, thus in this way for example, increasing the secretion of a part of the pancreas while decreasing the secretion of a different part at the same time. Another case where insulin repression may be convenient is to avoid an uncontrolled feedback loop in which insulin secretion causes the secretion of glucagon, which then releases more glucose from the liver. In a first method of reducing insulin secretion, beta cells are hyper-polarized, for example, by applying a DC pulse. In this way, cells will not respond to high glucose levels by depolarization and insulin secretion. It should be noted that the applied pulse does not need to be synchronized to the electrical activity. It is expected that hyper-polarization will be the last of a short while after the pulse is over. Possibly, only the length of the interval is increased, instead of stopping the activity of sudden increases completely. In a second method, the insulin stores of the pancreas are emptied, so that in later periods, the cells will not have significant amounts of insulin available for secretion. This emptying can be done for example, with the simultaneous provision of glucose or an insulin antagonist, to avoid adverse effects. The insulin, glucose or other pharmaceutical antagonist described herein can be provided in many forms. However, in an exemplary embodiment of the invention, they are provided by an external unit 116 or by an internal pump (not shown) in the controller 102. In a third method, the plate durations 144 are shortened, for example, when the islet cells are advanced excessively, in such a way that there is less time available for the influx of calcium. Alternatively, the periods of intra-depolarization may be extended, by hyper-polarizing the cells during repolarization and after the calcium channels are closed (or forced to close by hyper-polarization). This hyper-polarization will retard the appearance of the next depolarization and in this way, will reduce the total influx of calcium over a period of time. Alternatively or additionally, a hyper-polarization pulse may be applied during a sudden increase, to shorten the sudden increase.

AFFECTATION OF INSULIN PRODUCTION It is believed that various feedback mechanisms are linked to the electrical activity of beta cells and the production of insulin. In an exemplary embodiment of the invention, these feedback mechanisms are manipulated to increase or decrease the production of insulin, alternatively or additionally to directly control insulin secretion. In an exemplary embodiment of the invention, beta cells are prevented from secreting insulin, for example, by applying a hyper-polarization pulse. In this way, the intra-cellular stores remain full and less insulin is produced (and in this way less insulin can reach the bloodstream). In an exemplary embodiment of the invention, the beta cells are stimulated to release insulin. Depending on the cell, it is expected that if the cell is over-stimulated, it will be fatigued and require a significant amount of time to recover, during which time it will not produce insulin. If a cell is under-stimulated, it is expected that over time it will produce less insulin, as it adapts to its new conditions. If a cell is stimulated too much, it will continuously produce insulin at maximum speed.

CONTROL OF PANCRETE RESPONSE In an exemplary embodiment of the invention, instead of directly controlling the levels of insulin secretion, the response parameters of the pancreas are modified so that they directly respond to glucose levels. A parameter that can be varied is the response time. Another parameter is the gain (amplitude) of the response. In some situations, these two parameters can not be separated. However, it should be noted that by providing complete control of the pancreas, many different response profiles can be provided directly by the controller 102.

In an exemplary embodiment of the invention, the response time of the pancreas is increased or reduced by blocking or priming the rapid responding portions of the pancreas, in patients having both fast and slow response portions. Blocking can be achieved, for example, by partial or complete hyper-polarization. Priming can be achieved, for example, by applying a pulse below the threshold, for example, just before depolarization. One potential advantage of this pulse below the threshold is that it can use less energy than other pulses. The gain of the response can be controlled, for example, by blocking or by priming parts of the pancreas, to control the total amount of pancreatic tissue that takes part in the response. It should be noted that priming "decreases the response" of the cells making them act as fast response cells, thereby increasing the gain of the rapid response. In some cases, priming and / or blocking may need to be repeated periodically, to maintain the sensitivity profile of the pancreas as described. Alternatively or additionally, the sensitivity of the pancreas can be increased (or decreased) by supporting (or avoiding) the propagation of action potentials, for example, by providing a suitable pharmaceutical product. Octonal and Heptonal are examples of pharmaceutical products that > uncouple the separation connections. In an alternative embodiment of the invention, the secretion and / or production capacity of part or all of the pancreas is modified by controlling the blood flow to and / or from the pancreas. It is conjectured that the reduction of blood flow to the pancreas will reduce the rate of production and / or secretion of various pancreatic hormones. Alternatively or additionally, by preventing the hormone-laden blood from leaving the pancreas, the local concentration of different hormones increases and exhibits a greater secretion improving, or inhibiting the effect (as the case may be) for other hormones. It should be noted that in type II diabetes, the pancreas responds to increased glucose levels by providing increased levels of insulin. However, this response is delayed and therefore increases in magnitude. As a result, or due to a different mechanism, the body's response to insulin is reduced and / or delayed, forcing an even greater insulin production. In an exemplary embodiment of the invention, control of the pancreatic response is used to prevent this feedback cycle from occurring. In one embodiment of the invention, the pancreas is prevented from secreting increased amounts of insulin. Alternatively or additionally, glucagon secretion is reduced when previous glucose levels are increased (for example, at a user's indication before feeding) which prevents (or reduces) a maximum fasting glucose from being present at feeding. Alternatively or additionally, gastric emptying is delayed, for example, electrically or by using a pharmaceutical control. In an exemplary embodiment of the invention, when an abnormal response of the pancreas is detected or expected, one or both of the following actions may be performed: (a) suppress the pancreatic response; and (b) increase the pancreatic response (e.g., the reduction of insulin and / or glucagon secretion) to make it faster and / or more than usual, to quickly reverse the physiological situation for which an abnormal response is expected. In addition, according to some embodiments of the invention, the selective control of hormones allows a patient to be provided with selective hormonal rates, for example, by providing a glucagon-to-insulin ratio greater (or less) than It could be without electrical stimulation. It should be appreciated that in some cases, the independent control of hormones and / or glucose levels is not possible due to a biological coupling. However, by using the methods described herein, relative control is possible by reducing the coupling. In some cases it is expected that the reduction of overreaction by the pancreas may allow the pancreas to heal and reduce or make evident the need for other continuous treatment. Optionally, the controller 102 tests this possibility periodically, without applying its control or by reducing a degree of control and determining whether the pancreatic response is normal.

CONTROL WITHOUT INSULIN Alternatively or additionally to control the secretion of insulin production, the secretion and / or production of other pancreatic hormones can be controlled. These exemplary hormones include glucagon, somatostatin and pancreatic poly-peptide (PP). The levels and / or the level profile of these hormones can be controlled as long as insulin levels are controlled or while insulin levels are allowed to change without direct control. Thus, in some embodiments of the invention, hormones can be partially controlled independently of insulin. It should be noted that in some cases, control of factors other than insulin will indirectly control insulin levels. For example, the reduction of glucose levels in general will cause a reduction in insulin levels. Similarly, some of the pancreatic hormones interact via biological feedback mechanisms, for example, an increase in glucagon also increases insulin. These interactions can be represented using a set of the equation. In some modalities, a neural network can be used. In an exemplary embodiment of the invention, use is made of the fact that the feedback equations are not linear. Instead, the equations typically include a time delay and different gains for different relative hormone levels. In addition, the physiological mechanisms may depend on glucose levels, or nervous simulation, on the anterior activity of the pancreas and / or on various digestive hormones. The particular equations and / or parameter of the equation for a particular patient may need to be determined for that patient, for example, by controlled experimentation (for example, by modifying a hormone level and tracking the effect on others) or by observation. Once the equations are known, substantially independent (or less interdependent) control of one hormone relative to others to other hormones may be possible. For example, instead of providing a large increase in insulin, which will increase glucagon levels, a smaller increase, over a prolonged period of time, may have a similar effect on blood sugar, without causing the secretion of glucagon ( that could be confused with glucose that decreases the effect of insulin). Alternatively or additionally, the increase in glucagon (or, inversely, insulin or other pancreatic hormones) is performed as a series of short surges, with periods remaining between surges. In this way, even if the secreted hormone performs its activity, it must not increase in the blood and / or pancreatic cells, to levels that cause a significant secretion of the antagonistic hormone. As examples of various levels of lower interdependence, a ratio between the levels of hormonal secretion to a given physiological state (for example, glucose level) can be changed by at least 10%, 20%, 30%, 40% or more, increasing or decreasing, with the originally higher level as the denominator.

Alternatively or additionally, pharmaceutical products can be used to reduce the sensitivity of a cell type relative to other cell types (or to increase sensitivity), thus modifying the feedback equations and allowing some decay in the selective control of hormones. Alternatively, the 'responses' of the cells can be regulated by the pharmaceuticals, thus all cell types will respond in a more uniform manner. Exemplary pharmaceuticals that selectively affect pancreatic behavior include streptozotocin and alloxan, which reduce the production of insulin from beta cells and various drugs used for the treatment of diabetes. Alternatively or additionally, the pharmaceutical products that are provided block the receptors for the hormone that will be selectively deactivated. Alternatively or additionally, pharmaceuticals, for example antibodies, deactivate the hormone in the bloodstream. Exemplary pharmaceutical products are described, for example, in J Biol Chem February 11, 2000; 275 (6): 3827-37, Crystallogr D Act Biol Crystallogr May 2000; 56 (Pt 5): 573-80, Metabolism June 1999; 48 (6): 716-24, Am J Physiol January 1999; 276 (1 Ptl): E19-24, Endocrinology November 1998; 139 (11): 4448-54, FEBS Lett May 12, 2000; 473 (2): 207-11, Am J Physiol August 1999; 277 (2 Pt 1): E283-90, Cur Pharm, April, 1999; 5 (4): 255-63 and J Clin Invest April 1, 1998; 101 (7): 1421-30, the expositions thereof are incorporated herein by reference. Alternatively or additionally, as different parts of the pancreas have different proportions of cell types, a differential modification of a hormone with respect to other hormones can be achieved by selectively stimulating certain portions of the pancreas and / or selectively blocking the activity of portions of the pancreas. pancreas. Alternatively or additionally, the response of different cell types to the same stimulation of electric fields may be different, thereby allowing differential control of different hormones. A distinction must be made between the control of hormone levels and the control of glucose levels by causing the secretion of hormones. The glucose level control 'at least avoids the damage to the body caused by high or low glucose levels, however, it does not guarantee the availability of glucose to the cells of the body. Maintaining adequate hormone levels, on the other hand, can not only keep glucose within a desired variation, but also ensures that a sufficient level of insulin is available in such a way that the cells of the body can assimilate glucose. Additionally, various convenient bodily effects caused by hormones can be achieved, such as, for example, the control of fat and protein metabolism or the prevention of insulin tolerance. It should be noted that in some cases a hormonal ratio or a temporary hormonal profile is desirable, rather than a simple hormonal value. These effects can be achieved, for example, by temporarily varying the control of hormones. In an exemplary embodiment of the invention, a reduction in glucose levels is achieved by indirectly activating glucose transporters that do not depend on insulin. This effect may result from the direct local stimulation of neural afferent trajectories in the pancreas (or close to it) or from the enhanced activity of the pancreas (resulting from stimulation) that is detected by these local afferents. The neural signal that is reduced may include activation of GLUT that does not depend on insulin in remote tissue of the body, thereby increasing glucose uptake and reducing blood glucose independently of insulin or in parallel with a low, temporary or local secretion of insulin in the pancreas. Hormonal trajectories are also possible. A recent article shows that the stimulating cells in the heart can increase the absorption of glucose by the cells. - The existence of neural trajectories that stimulate cells (for example, such as, for example, the heart) are also well known. The article is "Contraction-Induced Fatty Acid Translocase / CD36 Translocation in Rat Cardiac Myocytes Is Mediated Through AMP-Activated Protein Kinase Signaling", in Diabetes July 2003; 52 (7): 1627-34, by Luiken JJ, Coort SL, Willems J, Coumans WA, • Bonen A, Van DerVusse GJ, Glatz JF, Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht , the Netherlands and the Department of Kinesiology, University of Waterloo, Waterloo, Canada, the exhibition of which are incorporated herein by reference.

INDIRECT CONTROL OF INSULIN In an exemplary embodiment of the invention, insulin levels are indirectly controlled by reducing glucose levels. In an exemplary embodiment of the invention, glucose levels are reduced using electrical stimulation as will be described below. As a result, insulin levels are reduced and / or do not increase significantly. In an exemplary embodiment of the invention, electrical stimulation reduces glucagon levels. Alternatively, some other path is used and when insulin levels decrease, so do glucagon levels. In an exemplary embodiment of the invention, insulin levels are increased and / or glucagon levels are reduced prior to feeding such that feeding does not cause a rapid rapid increase in glucose levels. LOGIC FOR EXAMPLE CONTROL Figure 3A is a flowchart of a logic scheme for example control 200, according to an exemplary embodiment of the invention. In this scheme, the intensity of pancreatic activity (and associated damage) is increased with the increase in glucose level. The various methods for increasing and decreasing pancreatic activity were described in greater detail above or below. Alerts are optionally provided to the patient at extreme glucose levels. In addition, the method may prefer to have an error and cause hyperglycemia whose adverse effects are less critical than those of hypoglycaemia, whose adverse effects are immediate. It should be noted that the logic for automatic control for controlling glucose levels has been developed previously for insulin pumps and can also be applied to controller 102. An added capability of controller 102 is to suppress the body's own production of insulin. An added limitation of the controller 102 - optionally takes into account to avoid the damage of the pancreas with an over-stimulation. In step 202, the glucose level is determined. Many methods can be used to determine the glucose level. In an exemplary embodiment of the invention, in cases of hyperglycemia, the measurement is repeated several times before starting the treatment. In cases of hypoglycemia, measurements are repeated a few times or not at all, before starting treatment. The treatment cycle is optionally repeated every two to five minutes. Alternatively, in critical situations, such as, for example, hypoglycaemia, the cycle is repeated even more frequently. If the glucose level is below 60 (mg / dL) (step 204), the production of additional insulin is optionally suppressed (206) and, optionally, the patient is alerted (208).

If the glucose level is between 60 and 150 (210), no action is taken, since these glucose levels are normal. If the glucose level is between 150 and 200 (212), the action taken depends on the previous action taken and the glucose level measured above. If, for example, the previous level was higher, the insulin secretion activity can be maintained or reduced. If, on the other hand, the glucose level was lower, the level of insulin secretion can be increased. For example, a pulse application ratio of 1: 3 between sudden increases that are modified and sudden increases that do not change can be provided (214) if the glucose level is now reduced from its previous measurement. It should be appreciated, of course, that the exact glucose levels and pulse parameters used for a particular patient will depend on the patient's medical history, but also on the particular response of the patient to the pulse parameters used. Some patients do not respond, as well as other patients and a more powerful pancreatic activity modification program is used. If the glucose level is between 200 and 250 (216), the action taken (218) may depend on the previous action taken for example by providing a rate of application of pulses between 1: 1 and 1: 2. Alternatively or additionally, the action taken may depend on the degree of change, direction or change and / or rate of change of glucose levels. Optionally, a model of insulin secretion, digestion and / or effect on blood glucose level is used to assess the significance of changes in glucose level. If the glucose level is between 250 and 300 (220), an even higher pulse application rate, such as for example 1: 1, can be applied (222). Glucose levels greater than 300 can be very dangerous. In this way, if these high proportions are determined, a faster rate of advance, the sudden increase or the individual action potentials can be applied (224). Alternatively or additionally, a non-excitatory pulse is also applied to improve secretion to at least some of the advancing pulses. If the level is greater than 400 (226), a bi-phasic advance pulse may be provided for the individual action potentials (228). It is expected that this pulse in its first phase induces depolarization and in its second phase extend a plate duration in such a way that the influx of calcium is increased. Alternatively or additionally, if not previously applied, a control of multiple pancreatic regions can be provided, to increase the total portion of the pancreas that will be used to secrete insulin at a higher rate. If the glucose level is higher than 500 (230), emergency measures may be required, for example, alerting the patient or his / her doctor (232) and emptying all available insulin in the pancreas (234). An available insulin storage can be maintained in the pancreas or in the device 102 (or an associated insulin pump) just for these cases. It should be noted that the previous method is only an example. For example, the exact action in each one can be modified, such as the mixing of actions, the pulse parameters and the delays before the change action. This control method uses circuits to control delayed closed cycles. Alternatively, open cycle circuits may be provided, which are similar to the handling of conventional glucose levels. In this cycle, the amount of insulin production from a particular pulse application is known and applied in response to an infrequent measurement of the glucose level, for example, using a blood test. The periodic test of glucose levels can be applied to detect a faulty control. The intermediate control cycles, the control circuits having a smaller delay and combined control cycles (which have both an open cycle and a closed cycle) can be used in other example embodiments of the invention.

LONG-TERM AND SHORT-TERM CONSIDERATIONS When electrification pulses are applied in accordance with the exemplary embodiments of the invention, both short-term and long-term effects are optionally considered. Short-term effects include, for example, effects on insulin secretion and production. Long-term effects include, for example, the effects on the viability and capacity of the tissues and the polarization of the electrodes. As will be described below, the long-term effects may be negative, such as, for example, cell death, or positive, such as, for example, health preparation or stimulation. The polarization and incrustation of the electrodes is optionally avoided when using ionic electrodes and when applying balanced pulses (with almost equal positive and negative charges). Alternatively, it is 946 they can use special coated electrodes, such as, for example, those coated with iridium oxide or titanium nitride. Alternatively or additionally, relatively large electrodes may be used. The balance can be on a pulse basis or it can be spread through various pulses. In an exemplary embodiment of the invention, the controller 102 stores in a memory associated therewith (not shown) a record of the glucose levels, the applied electrical and / or pharmaceutical control, the food ingestion and / or the effect of the control applied on the electrical activity of the pancreas and / or the effects on the blood glucose level. It should also be noted that as the disease progresses over time, certain cell types, for example beta cells, may die, so different methods and / or stimulation protocols may be suitable for different stages of the disease. . For example, the improvement of insulin secretion at the beginning of the disease and the reduction of glucagon secretion in the later stages of the disease. Other treatment protocols may be less affected by the progress of the disease, for example, the activation of GLUT that does not depend on insulin.

CELLULAR PREPARATION In an exemplary embodiment of the invention, applied electrification and / or pharmaceutical profiles are used to modify the behavior of cells in islets, in essence, preparing the cells to adapt to certain conditions. It is expected that the light stressing of a beta cell will cause the cell to compensate, for example by lengthening or by causing new beta cells to be produced. It is known that this mechanism of regeneration exists, for example as described in "Amelioration of Diabetes Mellitus in partially Depleted Rats by poly (ADP-ribose) synthetase inhibitors." Evidence of • Islet B-cell Regeneration ", by Y Yonemura et. al, in Diabetes; 33 (4): 401-404, April 1984, the disclosure thereof is incorporated herein by reference. An excess of tension can exterminate the cells. In this way, the level of tension that improves the functioning of the cells may need to be determined by trial and error for each patient. In an exemplary embodiment of the present invention, the test and errors are performed in different parts of the pancreas, optionally with a shunt for a sub-voltage instead of an over-voltage. In an exemplary embodiment of the invention, the over-voltage is determined by a marked reduction in insulin production or by a reduced or abnormal electrical response. Alternatively or additionally, a pancreatic cell that is not sensitive to average levels of glucose can be prepared to be sensitive to lower levels of glucose, by exciting it more frequently and / or by exciting it at times of slightly elevated glucose levels. . In an exemplary embodiment of the invention, these preparation pulses are applied in combination with the pharmaceutical products judged to cause regeneration or healing. It should be noted that the matching preparation and activation profile can also be used to maintain a cell in form in a patient who is temporarily being administered insulin, or to support a cell that is in recovery, for example, from a toxic material or from the onset of diabetes. Possibly, an electrical stimulation increases the intra-cellular calcium levels and as a result increases the genomic activity in the cell. This can increase the repair. However, too much increase can cause cell death by various mechanisms. Thus, in some embodiments of the invention, a relaxation time is provided for the pancreatic cells, to allow these levels to decrease. In other modalities and / or cases, this relaxation is not provided.

EXAMPLE ADDITIONAL LOGIC Figure 3B is a flowchart of another logic scheme for example control 240, according to an example embodiment of the invention. Figure 3B is similar to Figure 3A, however, Figure 3B shows a lower degree of discrimination between glucose levels, for clarity of presentation. The reference numbers of Figure 3B are 40 more than for the corresponding elements of Figure 3A. Figure 3B illustrates the control of hormone levels, • increasing glucagon secretion and selecting a protocol or treatment parameter. based on the effect on pancreatic hormones other than insulin. In response to a sensitization of glucose levels (242), if the level is low, presenting hypoglycemia, the secretion of "." • • • • • • -insulin (246) is optionally suppressed. Alternatively or additionally, the secretion of glucagon (245) 'is increased. If glucose levels are normal (250), an additional test is optionally performed to determine if hormone levels are normal or not (251). In an exemplary embodiment of the invention, hormone levels (e.g., insulin and / or glucagon) are measured directly using suitable detectors, e.g., fiber optic detectors or chemical analysis detectors of limited use. Alternatively or additionally, it is estimated that the levels are based on the variation of the blood glucose levels and / or the electrical activity of the pancreas. If the hormonal levels are very low, they decrease (253). Possibly, if the hormonal levels are very high, the stimulation is stopped and / or even suppressed (not shown). Possibly, a control logic similar to that of Figures 3A and 3B is initiated by a sensitization of the hormonal levels. The omission elements 252 to 258, which are the same as those of Figure 3A, if the glucose level is high and a rapid response is desired, a test is performed for which a plurality of available treatments and / or parameters are preferred. of the treatment (260). One question is which treatment will cause the secretion of glucagon, which secretion will frustrate the desired effect of glucose reduction. In any case, if after a suitable time delay the glucose levels (266) have not decreased, a more drastic treatment is applied.

ARTIFICIAL GAIN LOGIC Figures.3A and 3B show, among other things, a progressive logic in which, as the glucose level increases, a more drastic treatment is used. For some disease conditions, the pancreas may be able to respond correctly, however, the pancreas is not so sensitive to detection that its response is delayed and / or less than it should be for changes in the pancreas. blood glucose levels and / or cases of digestion. In other disease conditions, the pancreas has the ability of a slower second response (for example, raising insulin levels sufficiently after several tens of minutes) but not of an initial response (for example, a bolus of fasting insulin). in a few minutes). In an exemplary embodiment of the invention, the controller 102 is used to ensure that the pancreas responds (as indicated below) with a sufficient delay of amplitude and / or minimum. In an exemplary embodiment of the invention, the controller 102 detects gastric activity, identifies it as a digestive behavior or as the release of food from the stomach and therefore stimulates the pancreas to secrete a bolus of insulin and / or reduce glucose in another way. Alternatively or additionally, the stimulation decreases the sensitivity threshold of the pancreas in such a way that it responds adequately to natural stimuli, that is, that it does not respond excessively. Alternatively or additionally, stimulation causes the pancreas to increase its response to increased glucose levels, when your natural response is very low. It is specified that a large initial bolus of insulin, can have a non-linear effect on the body, for example, causing a rapid interruption of glucose secretion by the liver, or interruption of the release of glucagon by the pancreas. The non-linear effect may depend, for example, on the total amount of insulin and / or its rapid onset. In addition, the total effect of this bolus may be to reduce the amount of insulin actually secreted by the pancreas. Optionally, this bolus is applied before ingestion (for example, 5, 10 or 20 minutes before), for example, to interrupt in advance the secretion of glucose by the liver.

It should be noted that a normal pancreas is expected to exhibit an acute response to a case of ingestion by providing an initial bolus of glucose and causing the interruption of glucose secretion by the liver (although, at a time delay). A disadvantage of some pharmaceutical treatments is that maximum values of insulin and glucose are possible during the day. In an exemplary embodiment of the invention, a significant number of these maximum values are avoided and / or reduced by using the controller 102. For example, at least 20%, 40%, 60%, 80% or more of the maximum values are can reduce to 50%, 70% or more relative to the initial values.

OPEN CYCLE LOGIC For at least some stimulation pulses according to an example embodiment of the invention, over stimulation has minor and / or less harmful side effects than under stimulation. In some embodiments of the invention, this reduction in side effects is used to design the control schemes with the error on the side effect of the overstimulation, that is, the open cycle and partial open cycle control, with a bypass ascendant instead of a sub-esti ulation. By partial open cycle it must be understood that the decision if applied to a series of pulses is made periodically (for example, after ten minutes, half an hour, one hour or more) based on various cases. However, once a decision is made, detailed measurements are not used to provide feedback on the effect of the pulse for the purpose of modifying it. Once the series is completed, the decision to apply a new series of stimulation can be made. By open cycle it is necessary to understand that series of pulses that is applied using a fixed protocol without verifying its total effect. In particular, some of the pulse series described below will not require synchronization with pancreatic activity nor will it be necessary to measure the electrical activity, at least not during the application of the series of pulses. In an example of a relatively safe series of pulses, as shown below, some types of electrical stimulation reduce high glucose levels but practically do not reduce normal glucose levels. In another example, the general suppression. of the pancreas when glucose levels are almost normal (or even increasing in some cases) can prevent the secretion of insulin and / or glucagon which could disrupt the balance. In an exemplary embodiment of the invention, open-cycle stimulation is used to reduce glucose levels before digestion and / or during the digestion of a meal. In another example, open-cycle stimulation is used to periodically or semi-continuously reduce glucose levels. In these example modalities, a series of pulses is used as will be shown below, which practically does not affect normal glucose levels. In an example embodiment of the invention, a user has an external controller, for example, an optical detector for magnetic control or RF that communicates the fact of eating with the controller 102. Optionally, it sends a signal (for example, to decrease the glucagon secretion) before eating, thus stopping the secretion of glucose by the liver (eg, as a result of an increase in glucagon or other mechanism) can take tens of minutes. Another safety feature of a stimulation according to some embodiments of the invention is that the prolonged stimulation appears to have no significant side effects on any of the pancreatic viability, pancreatic endocrine function and pancreatic exocrine function.

FORMS AND PARAMETERS OF PULSES The variation of the forms of pulses that can be applied profitably is very wide. It should be noted that the response of cells in different patients or of different cells in the same patient, even for the same pulses, it is expected to differ considerably, for example, due to genetics and disease status. Also, the conduction of electrical signals in the vicinity of the pancreas is affected by the irregular geometric shape of the pancreas and the layers of fat that surround it. These insulating layers may require the application of higher amplitudes than expected. It should also be noted that, at least for some modalities, the application of the pulse is to affect a certain portion of the pancreas and not the entire pancreas. The lack of a significant spread of action potentials from one islet of the pancreas to another may require a relatively uniform field in the portion of the pancreas that will be affected. However, completely uniform fields are not required since any edge effects are contained only for the islands with the intermediate electric field resistances and / or because the cellular behavior is expected to not vary sharply with the amplitude applied, except maybe at certain threshold levels. In addition, the behavior of the beta cells may depend on the level of glucose, on the level of storage of cellular insulin and / or on the previous activity of the cells. Unlike cardiac cells, which function continuously and typically at a limit of their capacity and / or oxygen utilization, normal pancreatic cells with large surpluses are provided and operated at sub-peak levels. A first pulse parameter is either AC or DC. As the pulse is applied periodically, the term DC pulse is used for a pulse that does not alternate in amplitude considerably during an individual application, while an AC pulse, for example, does not have an intrinsic frequency of an order of magnitude greater than duration of 1 / pulse. In an exemplary embodiment of the invention, DC pulses or pulses having a lower number of cycles per application are used. In this use, a pulse that is synchronized to a sudden increase is considered AC if it alternates in amplitude, for example, ten times over the duration of the sudden increase, even though this frequency really is <; • -lower than the frequency of action potential. If, on the contrary, the pulse is a square pulse synchronized with the individual action potentials, a DC pulse will be considered for this analysis, although its actual frequency is greater than that of the AC pulse. The example frequencies for AC pulses applied in sudden increments are between 1 and 1000 Hz and for AC pulses applied to action potentials, between 20 and 2000 Hz. Optionally, AC frequencies are between 50 and 150 Hz. Various pulse durations can be used. One advantage of a long-lasting DC pulse is the lack of momentary currents that could unintentionally affect other tissues. It is expected that this pulse will be useful for the hyper-polarization of cells and, in this way, may be the last for several seconds or even minutes or hours. Optionally, however, pulses of very long duration are interrupted and possibly their polarity is switched to avoid adverse effects such as, for example, polarization of tissues near the electrodes or over-polarization of the target tissue. A pulse to affect a sudden increase may be, for example, at least between 1 ms and 100 seconds. The example durations are 10 ms, 100 ms and 0.5 seconds. Longer pulses may be between \ eg 2 or 20 seconds long. A pulse to affect an individual action potential in general will be considerably shorter, for example being between 10 and 500 ms long. The example durations are 20, 50 and 100 ms. However, larger pulses, such as for example 600 or 6000 ms in length can also be applied. In AC pulses, various utilization coefficients may be used, for example 10%, 50%, 90% and 100%. Percentages may reflect pulse on / off time or may reflect relative charge densities during on and off times. For example, a 50% utilization coefficient may be provided, on average, 50% of the maximum pulse load flow. A pulse can be unipolar or bipolar. In an exemplary embodiment of the invention, balanced pulses are used, which have a total zero charge transfer. Alternatively, however, the equilibrium can also be achieved through a pulse preparation or over a longer period. It is expected that at least for some pulse effects, the islets will act independently of the polarity of the applied pulse. However, polarity changes can still have convenient effects, for example, when creating ion currents. It is known that different pulse envelopes interact with cell membranes in different ways. The pulse envelope can be, for example, sinusoidal, triangular, square, exponential decay, bi-phasic or sigmoid The pulse can be symmetric or asymmetric Optionally, the pulse envelope is selected to take into account variations in impedance of tissues during the application of the pulse and / or efficiency and / or simplicity of the energy electronics In an example embodiment of the invention, the pulse current is controlled, for example, which remains within a variation. or additionally, the pulse voltage is controlled, for example, to remain within a variation.Alternatively or additionally, both the current and the voltage are controlled at least partially, for example, they are maintained in certain variations. It is defined by its total charge Different types of pulses in general, although not necessarily, will have different amplitudes The different effects of the pulse also They can be a function of the phase in cellular activity and especially the sensitivity of the cell to electric fields at the time of application. The types of pulse amplitude of example, are pulses below the threshold that affect the depolarization state of the cell and the pulses that affect the channel. These pulses are non-limiting examples of non-excitatory pulses, that do not provoke a potential of action of propagation in the island, either due to an absolute amplitude to low or due to a low relative amplitude (in relation to cellular sensitivity). A stream in the 5 pA island is suggested in the Medtronic PCT publication for stimulating pulses. The forward pulses definitely cause a propagation of the action potential, unless the forward pulse captures all the cells in the island, in which case there will be no place for the action potential to propagate. The pulses of "defibrillation" are stronger than the pulses of advance and cause a surplus in the electrical status of the affected cells. Pore-forming pulses, for example, high-voltage pulses, create pores in the membrane of affected cells, allowing calcium to be spilled inside or outside and / or allowing insulin to leak. The above pulse types are listed in order of typical amplitude increase. The example amplitudes depend on many factors, as noted above. However, an example feed pulse is between 1 and 20 mA. A non-excitatory pulse of A. '112, " example is between 1 and 7 mA. A pulse below the threshold, for example, may be between 0.1 and 0.5 mA. It should be noted that the lack of excitation may be due to the timing of the pulse application. Simple pulse shapes can be combined to form complex pulse configurations and essentially to form pulse sets. An example of a pulse set is a double forward pulse (two pulses separated by a delay of 20 ms) to ensure the capture of a forward signal. Another example of a set of pulses is an advancing pulse followed, in a short delay, by a pulse for extension in plates and / or other pulses for control of action potential. In this way, not only the advance is forced, possibly at a higher speed than normal, but also the efficiency of each action potential is increased. The delay between the advancing pulse and the pulse for controlling the action potential may depend, for example, on the shape of the action potential and especially on the timing of the opening and closing of the different ion channels and pumps. The example delays are 10, 50, 200 and 400 ms. In some embodiments of the invention, a graduated pulse is applied. A first part of the pulse first blocks the cells that respond to a second part of the pulse. This pulse can be used, for example, to differentiate between different types of cells, between cells that have different levels of stimulation and / or between cells that have a rapid response and cells that have a slow response. The exact behavior of that pulse and / or suitable parameters can be determined during a preparation step, described with reference to Figure, 7, below. With the exception that different experiments were performed on different species of animals, at different stages of life, the experimental one seems that as one of the general rule pulses 20 Hz and 100 Hz, under some parametric adjustments, induces new sudden increases (and increases insulin secretion). Pulses of 5 Hz, at least in situ do not seem to induce new sudden increases and therefore are not excitatory. A particular pulse of 5 Hz shown reduces glucose without substantially increasing, or even decreasing insulin is a bi-phasic pulse, with each phase being 5 ms long and 190 ms between individual pulses, ie a carrier of 5 Hz. This pulse is applied without the synchronization of pancreatic electrical activity. While the series of pulses can be applied continuously for several minutes, some pulses are applied for short periods of time, such as, for example, one second each minute and they seem to have an intensifying effect on the pancreas, for example, causing the pancreas responds more strongly to increased levels of glucose existing. In an exemplary embodiment of the invention, a pulse consisting of a short usage coefficient repeated at a low frequency, can be observed as a low frequency wave (e.g., 5 Hz) coated with a higher frequency wave (pulse bi-phasic of 10 ms duration). In an exemplary embodiment of the invention, a low frequency is used to carry the effects of the electric field on the pancreas. The higher frequency is used to carry the effects of the wave within individual cells, by creating a decrease in voltage on their cell walls. In an exemplary embodiment of the invention, the low frequency components of the pulses are selected to have a periodicity similar to that of pancreatic (normal) cells of the selected type. Alternatively or additionally, the pulse width (e.g., high frequency components) are selected to specifically target certain cell types, e.g., beta cells, alpha cells and nerve cells. For example, it seems, although it is not certain, that lower frequencies (for example, the 5 Hz component) affect the activity of the island and higher frequencies affect the neural trajectories. In addition, lower frequency pulses (eg, even DC) are used for cell hyper-polarization. It is known in this field that various optimization and research techniques can be used, especially to find optimal pulses for a particular patient.

TIMES OF THE PULSES Not only diverse pulse forms are contemplated, but also different variations in their periodicity are contemplated. A first consideration is to synchronize or not an excitatory pulse and / or a non-excitatory pulse for pancreatic activity. If the pulse is synchronized, it is that it can be synchronized to the activity of the particular cells or islets that will be measured. As noted above, a forward pulse to the pancreas can force synchronization. The pulse can be synchronized for individual action potentials and / or for activity in sudden increments. Within an action potential, the pulse can be synchronized for different characteristics of the action potential, for example, depolarization, plating, repolarization and an inactive period before depolarization. Not all action potentials will exhibit exactly these characteristics. Within a sudden increase, a pulse can be synchronized at the beginning or end of the sudden increase or changes in the envelope of the sudden increase, for example, significant reductions in the frequency or amplitude of the action potential. In the sense in which it is used in the present, the synchronization to an event includes being applied to a delay in relation to the event that occurs or to a delay when the event is expected to be present (positive or negative delay). This delay may be constant or may vary, for example, depending on the action potential of the sudden increase activity. The pulse can be applied in each event to which it is synchronized, for example, each action potential or each sudden increase. Alternatively, the pulses are applied to events smaller than in general, for example, at a ratio of 1: 2, 1: 3, 1:10 or 1:20. An example reason for reducing the rate of application of pulses is to avoid over-tension of the beta cells and cause cellular degeneration, or to provide finer control over the time of secretion. In some pulses, a significant parameter is the frequency of application of the pulse (as it differs from the frequency of amplitude variations in an individual pulse). The example frequencies vary from 0. 1 Hz to 100 Hz, depending on the type of pulse. In an exemplary embodiment of the invention, the pulse parameters depend on the electrical and / or physiological state of the island or cell. This state can be determined, for example, by using suitable detectors that can be estimated from a global glucose level state. In an exemplary embodiment of the invention, the pulses are applied in a manner that provides an oscillating insulin secretion. These oscillations optionally mimic natural oscillations, with the controller being used to provide natural oscillations and / or changes in oscillation as they are typical of a healthy pancreas. Alternatively, the oscillations are exaggerated, for example, in amplitude or frequency or diffuse, for example, in amplitude or frequency. Oscillations can be provided, for example, by periodically increasing insulin secretion and / or by periodically increasing insulin secretion. Alternatively or additionally, the oscillations are presented by the advance that synchronizes the pancreas. Optionally, the treatment provided by the device 102 is designed to increase the natural oscillation behavior of the pancreas, for example, by learning in which the stimulation sequences increase is the behavior under one or more conditions.

DETECTORS Many types of detectors can be usefully used to provide a feedback for the controller 102, including, for example: (a) glucose detectors, for example, for the determination of the actual glucose level and provide feedback on the effects of the treatment pancreatic. Thus, for example, in a patient who has a weakened pancreatic response, the pancreas will be stimulated to secrete more insulin when the glucose levels are very high. Many types of glucose detectors are known in the art and can be used for the purposes of the present invention, including, for example, optical, chemical, ultrasonic, heart rate, biological (e.g., encapsulated beta cells) and electrical ( beta cell tracking and / or electrical behavior of the islets). These detectors can be inside or outside the body, connected to the controller 102 by wires or wirelessly, they can be in contact with the blood or outside the blood vessels. (b) digestion detectors, for example, to detect ingestion or next ingestion of food, and, for example, by initiating insulin production or increased cellular sensitivity. Many suitable detectors are known in the art, for example, impedance detectors that measure the stomach impedance, acceleration detectors that measure the movements of the stomach or intestines and electrical detectors that measure electrical activity. Digestion sensing cells are inherently problematic in some embodiments of the invention, and they do not provide a glucose measurement actually ingested. Optionally, they are used in combination with other detectors and / or only if the digestion system is activated in a profile that matches the feeding, for example, a long-lasting activation or an activation that advances along the digestive system. In an exemplary embodiment of the invention, stimulation during digestion can be stopped for at least some parts of the pancreas (for example, those comprising smaller islands), to avoid interfering with other cell types in the pancreas, for example , those that produce digestive juices. Alternatively or additionally, the stimulation application in general can be optimized to reduce the interaction with non-beta cells, for example, alpha cells. As alpha cells generate glucagon, their stimulation can be determined by tracking serum glucagon levels. As noted elsewhere in this application, in some cases, glucagon reduction is a convenient effect; and in some modalities it is expected that it does not interfere with the exocrine function. (c) detectors of pancreatic activity, for example, electrodes coupled to the total pancreas, small portions thereof, individual islets or individual cells in an island. These detectors are useful not only to provide a feedback on the activity of the pancreas either the applied pulses have a desired electrical effect (as opposed to glucose), but also for the synchronization of pancreatic electrical activity. Example detectors are described, for example, in PCT publication WO 03/045493, the disclosure thereof being incorporated herein by reference. (d) calcium detectors, both for intra-cellular spaces and for extra-cellular spaces. As can be seen, the measurement of calcium within a cell can affect the behavior of the cell. In an exemplary embodiment of the invention, only a few cells are used as a sample for the state of the other cells. An example method for measuring intra-cellular calcium is to stain the cell with a calcium-sensitive dye and to track its optical characteristics. It should be noted that both intra- and extra-cellular levels can affect the electrical and secretory activity of beta cells. (e) insulin detectors of any type known in the art can be used to measure the individual response, the pancreas as a whole and / or to determine blood insulin levels. (f) detectors for other pancreatic hormones, for example, for glucagon and / or somatostatin. As will be mentioned later, in some cases the various levels of pancreatic hormones can be estimated based on changes in blood glucose levels, the changes correspond to the changes observed previously during which hormonal levels were measured. The measurements of the above detectors are optionally used to modify the pulse parameters or the rate of application of pulses. Alternatively t or additionally, the detectors are used to track the response to the regime and / or lack of pulse application, or for calibration. Different detection regimes can be used, including continuous detection and periodic detection. Some detectors can provide a frequent measurement, for example, every few seconds or minutes. Other detectors can be considerably slower, for example, when tracking a measurement every ten minutes or an hour. If only a periodic measurement is required, measurements can be an average over time between measurements or can be an average over a shorter time or an instantaneous value. In some cases, a long-term integrative sensitization, for example, of insulin production, is desirable. For this integrative sensitization a single-use chemical detector may be convenient. Various methods of sensitization and detectors are described, for example, in U.S. Patent No. 6,600,953, PCT publication WO 01/91854, U.S. Provisional Patent Application No. 60 / 259,925, the application for U.S. Patent No. 60 / 284,497, U.S. Patent Application No. 60 / 334,017, PCT / IL02 / 00007 Application, filed January 3, 2002, PCT Publication WO 02/082968 , PCT PCT publication WO 03/045493, mentioned above, and U.S. patent application serial number 10 / 296,668, all of which are hereby incorporated by reference. It should be noted that some of the sensitization methods described in these applications allow an estimate, for example, of a total glucose load, a rate of glucose increase and / or a delay until the glucose increase begins. This information can be used to properly configure the glucose control treatment so that it has a desired effect, for example, by adjusting the duration of stimulation and parts of the affected pancreas.

TYPES OF ELECTRODES The electrodes used can be electrodes with individual functionality, for example only for forward pulses or only for non-excitatory pulses. Also, different types of non-exciting pulses, such as, for example, hyper-polarization and plate-spread pulses, can use different types of electrode geometries. Alternatively, a combination of electrodes may be provided, comprising both a leading portion and a portion for applying pulses. The different types of electrodes can have different configurations, for example, because the advancing electrode will be designed for an efficiency and the pulse electrode will be designed for field uniformity. The two electrode functions can share the same derivation or can use different derivations. Alternatively, a single electrode shape is used for an application of both forward and non-exciting pulses. Figures 4A-4D illustrate different types of electrodes that may be suitable for pancreatic electrification, in accordance with exemplary embodiments of the invention. Figure 4A illustrates a point electrode 300 having an individual electrical contact zone at a tip 304 of a branch 302 thereof. Figure 4B illustrates an inline electrode 306 having a plurality of electrical contacts 310 along the length of a branch 308 thereof. An advantage of the wire and point electrode is an expected ease in implantation using minimally endoscopic and / or other invasive techniques. In an exemplary embodiment of the invention, multiple wired electrodes are implanted. Figure 4C illustrates a screen electrode 312, which includes a branch 314 and having a plurality of meeting points 318 of the screen wires 316. Alternatively or additionally, some wire segments between the meeting points provide elongated electrical contacts. Each of the contact points can be small, for example, slightly larger than that of an island. Alternatively, larger contact zones are used. For in-line electrodes, the example contact zones are 0.2, 0.5, 1.2 or 5 mm long. In some embodiments of the invention, minor contact areas that are used for cardiac pacemakers may be suitable, depending on - they may be - sufficient smaller fields. In some embodiments, a volume of excitation of the pancreas is desired. Figure 4D illustrates various electrodes for excitation volume. A plate electrode. 320 includes a plate 322 that can simultaneously excite a larger zone. A spherical electrode 324 that includes a spherical contact area 326, with a radius of, for example, 2 or 4 mm, to excite the tissue surrounding the sphere 326. A hollow volume electrode 328, for example, includes a open volume contact zone 330, 'for example, a screen sphere or a cup, which can be used to excite the tissue in contact with any part of the sphere 330, including 1? 6 its interior. Another possibility is a wound electrode. Optionally, the turns have a significant radius, such as, for example, 2 or 5 mm, in such a way that they enclose significant pancreatic tissues. It should be noted that the volumetric electrodes (and also other electrodes) can encompass a small or large portion of the pancreas or can even be located to electrify substantially all the insulin-producing portions of the pancreas. Any of the above electrodes can be unipolar or bipolar. In bipolar modalities, an individual contact zone may be invaded or bi-polar activity may be exhibited between adjacent contact points. In addition, the last contact ulti-contact electrodes can have all contact points shortened together. Alternatively, at least some of the contact points can be electrified separately and, optionally, independently, from other points of contact of the same electrode. The electrical contact between an electrode and the pancreas can be improved in many ways, for example, using a porous electrode, steroids (especially when using electrodes for steroid choice) and / or other techniques known in the art. The type of electrodes can be any of those known in i. • - •, 127 - the technique, and especially those designed for long-term electrical stimulation. Figure 4E illustrates a different type of electrode in which an envelope 332 of the controller 102 serves as one or multiple electrodes. The wrap 332 can be concave, convex or it can have a more complex geometry. Possibly, no external electrodes are used outside the wrap 332. Optionally, the wrap 332 is then concave, so that it receives the pancreas. Alternatively, at least one common electrode 336 is provided outside the controller 102. Alternatively or additionally, the envelope 332 of the controller 102 serves as a common electrode. In an exemplary embodiment of the invention, a plurality of electrodes 334 are formed in the envelope 332. For example, the electrode types can be any of those described above. Optionally, although not necessarily, the electrodes 334 exit the wrapper 332. In an exemplary embodiment of the invention, the controller 102 is placed in contact with the pancreas 100, as a layer of electrical grease insulation usually encapsulates the pancreas. Optionally, the geometry of the wrap 332 is produced so that it conforms to the configuration of the pancreas, thus ensuring contact with the pancreas and minimal trauma to the pancreas by implantation. Optionally, a flexible or multi-part hinged wrapping is provided to better conform to the envelope for the pancreas. The electrodes can be fixed to the pancreas by many means, including, for example, the use of one or more sutures b fasteners, providing turns or roughness in the body of the electrode, using adhesive by introducing the pancreas or nearby tissue. An electrode may include a cycle, an orifice or other structure thereon for securing the suture or fastener thereto. It should be noted that the pancreas does not move around like the heart, so that a less resilient electrode and bypass materials and binding methods can be used. Various combinations of the above electrodes may be used in a single device, for example, a combination of a screen electrode below the pancreas and an electrode with a ground needle above the pancreas. This ground electrode can also be inserted into nearby structures, such as, for example, the abdominal muscles. As will be described later, the pancreas can be controlled as a plurality of controlled regions. An individual electrode can be shared between different regions.

Alternatively or additionally, a plurality of different electrodes may be provided for the different zones and even for a single region. Optionally, the electrodes, or points thereof, are coated with a cortisone or other anti-inflammatory, to avoid an inflammatory response by the organ to which the 'electrode' is brought into contact.

REGIONS FOR PANCREATIC CONTROL Figure 5 illustrates a pancreas subdivided into a plurality of control regions 340, each region being electrified by a different electrode 342. The control regions 340 may overlap (as shown) or may not be superimposed. Possibly, the total pancreas is also a control region, for example, for the suppression of insulin secretion. Although a significant percentage of the pancreas is optionally controlled, for example 10%, 20%, 40% or 60%, part of the pancreas can remain uncontrolled, for example, as a control region or a safety measure. The number of control regions may vary, for example, two, three, four, six or even ten or more. In many of the experiments described below, it is estimated that between approximately 10% and 30% of the pancreas was activated.

A possible one of different control regions is to allow one part of the pancreas to rest while another part is stimulated for an effort of it. Another possible use is to test different treatment protocols in different regions. Another possible use is to provide different control logic for parts of the pancreas with different capacities, to better utilize regions or to avoid damage due to reasons. For example, different pulses can be applied to fast response or slow response portions. Also, some parts of the pancreas may be sicker than others. Optionally, the density and / or size of the placement of the electrodes in the pancreas (and the portions controllable independently of the electrodes) varies and depends, for example, on the distribution and density of the. Islet cells in the pancreas. For example, a section that is densely populated from the pancreas can be provided with a finer electrical control. It should be noted that the distribution may be the original distribution or it may be the distribution after the pancreas became diseased and some of the cells died or were damaged. As noted above, different parts of the pancreas can produce different types and / or relative amounts of various hormones. In this way, selective spatial control can be used to achieve a desired level and / or hormonal mixture.

METHOD OF IMPLEMENTATION The implementation of the controller 102 may include the implantation of electrodes and the implantation of the controller itself. Optionally, the two implantations are carried out as an individual procedure. . However, it should be noted that each implementation has its own characteristics. The implantation of a small envelope in the stomach is a well-known technique and can be performed, for example, using a laparoscope, using open surgery or using endoscopic surgery. The implantation of electrodes in the pancreas is not a standard procedure. Optionally, elongated electrodes are used, without coiling or without bending in such a way that the implantation of the electrode is simplified. In an exemplary embodiment of the invention, the electrodes are implanted using a procedure "laparoscopic or endoscopic" Optionally, also the controller 102 that inserts using a laparoscope or endoscope In an exemplary embodiment of the invention, the geometry of the controller 102 is that of a cylinder, such that it passes better through a endoscope (a narrow diameter, relatively flexible tube) or a laparoscope (a large diameter, relatively rigid tube) Alternatively, the controller 102 is implanted separately from the electrodes., the electrodes are implanted with a connection zone (for example, wire ends) of the electrodes readily available. A second optical detector input is made and the controller joins the connection zones. Possibly, the electrodes are implanted in a first connection portion. Alternatively, after the electrodes are implanted, the endoscope retracts, leaving the connection area in the body. Figures 6A and 6B are flow charts of implantation methods, according to exemplary embodiments of the invention. Figure 6A is a flow diagram 400 of a bile duct approach. First, an endoscope is taken to a bile duct, for example, through the stomach (402). The endoscope then enters the bile duct (404) for example, using methods known in the art. As shown, the endoscope can travel through the bile ducts along the pancreas. Alternatively, the electrodes can be provided by a catheterization of the splenic artery or vein. Alternatively, the portal vein can be catheterized, for example, via a laparoscopic opening in the abdomen. The electrodes are implanted inside, or along the pancreas, for example, in the blood vessels of the bile ducts, the pancreas will be an elongated gland (406). In an exemplary embodiment of the invention, the endoscope (or an extension thereof) is advanced first to the far end of the pancreas, the electrodes are attached to the pancreas and then the endoscope retracts, leaving the electrodes behind. Alternatively, the electrodes can be advanced out of the pancreas, by themselves or using a relatively rigid and / or navigable corset. Optionally, although not necessarily, imaging techniques are used, such as, for example, por-light imaging, ultrasound or X-rays, to track the electrode and / or the endoscope. Imaging can be performed from outside the body or from inside the body, for example, from the tip of the endoscope. Any damage to the body structures is optionally repaired during retraction of the endoscope / catheter (408). Alternatively, other arterial and / or venous techniques can be used. In some techniques, the controller 102 is implanted and then the electrodes are guided along or into a blood vessel or other body structure of the pancreas. In the implantation in the bile duct, a special coating can be provided on the electrode or leads, to protect against bile fluids. The contact portion of the electrode can be embedded in the tissue to prevent damage by bile fluids thereto. Figure 6B is a flow diagram 420 of an alternative implantation method. An endoscope is advanced into the duodenum or other portion of the intestine adjacent to the pancreas (422). The electrodes extend from the intestine into the interior of the pancreas (424), while the controller 102 remains in the intestines. The electrodes can also extend parts along the inside of the intestines. The electrodes on the far side of the pancreas can be implanted from a different portion of the intestines or can be passed through the pancreas. Alternatively, the controller is also forced out through a hole formed in the side of the intestines. Alternatively, the controller is enclosed in a corset of the intestines. The corset is optionally formed by suturing or holding part of the intestines. Alternatively, the controller is attached to the intestines, for example, using fasteners or using sutures. Then any damage to the intestines can be repaired (426). As noted above with reference to Figure 1, the controller 102 may be a wireless device, with the control circuitry separate from the electrodes. The electrodes can have individual energy sources or they can be energized (or recharged) using directed energy. In an alternative modality, the controller 102 is a multi-part device, for example, comprising a plurality of mini-controllers, each mini-controller that controls a different portion of the pancreas. The activities of the mini-controllers can be synchronized by communication between the controllers or by a master controller, for example, separately, possibly an external unit 116. The unit 116 can directly synchronize the mini-controllers and / or can provide a schedule to cause them to act in a synchronized way. An example geometry for a mini-controller is that of two spheres connected by a wire. Each sphere is an electrode, one sphere contains a source of energy and the other sphere contains the control circuitry. The communication between the mini-controllers for example, can be using radio waves, optionally low frequency, or using ultrasound. An appropriate transmitter and / or receiver elements (not shown) are optionally provided in the mini-controllers. Alternatively to an implanted controller, the controller may be external to the body with electrodes that are inserted percutaneously into the pancreas, or even remain on the external side of the body. Alternatively, the controller and the electrodes can be completely enclosed by the intestines. These "implantation" methods are sometimes preferred for the temporary use of the device. In some cases, the proper implantation of the detectors can be problematic, for example, the detectors that introduce individual beta cells or islets. In an optional procedure, a portion of the pancreas is removed, the detectors and / or electrodes are attached thereto and then the removed portion is inserted back into the body. In the above modalities, it was suggested to introduce the pancreas using electrodes or electrode guides. In an exemplary embodiment of the invention, when the introduction is made, care must be taken to avoid major nerves and blood vessels. In an exemplary embodiment of the invention, the implantation of. , -, • v. 1.37 ' Electrodes take into account other nearby excitable tissue and avoid inadvertent stimulation of that tissue. As will be discussed below, some experiments have shown that the application of an electric field to the stomach, using the parameters as described above, can cause the reduction of glucose levels. Without limiting the current application, it is conjectured that what is occurring is an electric field applied to the electrodes that extend to a significant portion of the pancreas (or other organ over which the field has the desired effect) and / or to the tissue nervous inside or near the pancreas. In. human beings, as well as pigs, the pancreas is located near the stomach. Optionally, the electrodes to electrify the pancreas are attached to the stomach. A potential benefit is that there is less damage from perforating the pancreas and / or causing inflammation or infection of the pancreas. Another potential benefit is that the stomach is a muscular organ and suturing or other methods of attachment are generally easier to apply, rather than the pancreas. This may also allow a greater number of electrodes and / or specificity to be used. Optionally, the controller itself joins the stomach. Another potential benefit of the stomach is that the same electrodes used to electrify the pancreas can also be used for the control of obesity, for example, as described in U.S. Patent Nos. 6,571,127, 6,630,123 and 6,600,953; United States Nos. 09 / 734,358 and 10 / 250,714 and PCT publication WO 02/082968, the teachings of which are hereby incorporated by reference. Another potential benefit of the stomach is that as the volume of the stomach is an insulator, any electric field in general will travel around the stomach (and therefore through or through the pancreas). Another potential benefit is that laparoscopic surgery for the stomach is well known. While some effect of the field on the stomach can be presented, optionally, the effect is minor and / or neutralized by applying a field to the stomach to correct the effect. Optionally, signals for pancreatic control are synchronized to the electrical activity of the stomach, for example, so that they have a minimal effect on the stomach. Optionally, the delay and / or duration of the sequence is optimized by experimentation, for example, to be 0, 1, 2, 4, 6 or another number of seconds, or intermediate or greater values. In particular, the pulse may be applied during a refractory phase or during a depolarization of the stomach (or other) smooth muscle. Alternatively or additionally, the delay and / or sequence period is varied such that there is no individual effect on the stomach (if any). Optionally, the delay is calculated using a local sensitizing electrode (may be the same as the stimulating electrode) at the application location. Alternatively or additionally, the expected or average activation time in another portion of the stomach is taken into account. Depending on the locations of the tissue to which the electrodes are attached, various inter-electrode distances may be used, for example, 1 cm, 2 cm, 3 cm, 4 cm or less, intermediate or greater values. As can be seen, the greater the distance, in general, the greater the field resistance at the points that are not directly between the electrodes. This is useful, for example, when the pancreatic tissue will be electrified and not directly between the electrodes. In some cases, the exact level of electrification of the electrode will depend on several factors, for example, the distance between the electrodes, the types of tissue, the properties of the tissue and the orientation of the electrode. Optionally, a calibration step is carried out in which a suitable field resistance is found. In one example, the current and / or voltage are varied in a staggered fashion over a ^ 0. series of tests until a significant effect is determined, for example, each step can be carried out under a different case of glucose ingestion. Optionally, the calibration is also used to determine that a few or no undesirable effects are being caused by the effect of the electric field on another tissue. The results of this calibration can be determined, for example, with the stimulation electrodes, simulation resistance, simulation polarity, timing (e.g., delay and / or duration), activators to stimulate or not stimulate (e.g. the colon is completely detected using an impedance detector), and / or the use of various possible sequences. Optionally, an insulation backing is provided over the electrodes to help direct the field. For example, a backup can be provided between an electrode and the tissue to which it is attached, to avoid or reduce the effect of the field on the tissue. In an exemplary embodiment of the invention, the backrest comprises a silicone pad of dimensions of 20 mm x 40 mm. Figure 6C illustrates example locations of the electrodes in a stomach 600 and / or a duodenum 604, near a pancreas 602. A plurality of electrode locations 610-632 are shown and many other locations are also possible. In addition to the organs shown, the union can be to one or more of the following organs: abdominal muscles, liver, other abdominal organs, other portions of the Gl tract, such as, for example, the small intestine or the colon, for example, the transverse colon, - the ligaments, blood vessels and / or fatty tissues. In general, the organs can be on any of the six cardinal sides of the pancreas. In the figure, the solid electrodes are above the organs and the electrodes in dotted lines are below the organ (for example, the stomach). The location of the example electrode, the electrodes 610-618 along the duodenum, the electrodes 620-624 along the stomach opposite the duodenum, the electrodes 626 and 628 near the center of the stomach, the electrode 629 near are shown from the upper part of the stomach, two lines of electrodes 630 and 632 in general along the pancreas on the far side of the stomach, a line of electrodes 634 diverted from electrodes 630 and a line of electrodes 636 between the pancreas and stomach. Other electrode locations can also be used, for example, in general any point on an organ surface near the pancreas or can be 14.2 place in such a way that there is a significant current through the pancreas. Optionally, electrodes with an electrification sequence will be provided in such a way that different organs and / or portions of organs are electrified to different pancreas stimulation sessions. Various electrode configurations can be used, for example, two electrodes with opposite polarities, or an electrode and the device coating, or pairs of electrodes, with opposite polarities or groups of electrodes where each group has the same polarity. It should be noted that depending on the selected electrodes, it is possible to intentionally electrify only a portion of the pancreas or selectively electrify different portions.Another issue that must be observed is that the figure shows point electrodes.While point electrodes can be used, as well as electrodes of sieve and zone, in an exemplary embodiment of the invention, the electrodes are wired electrodes.These wired electrodes can be curved or rolled in. Optionally, however, the wires are practically straight and have an orientation. for example, parallel, perpendicular or oblique to the pan you create and / or to each other (for example, in pairs of electrodes). When the electrodes that are the means to stimulate a pancreas join the stomach, the electrodes can be placed in the gastric muscle. Optionally, however, the electrodes are sutured to the muscle but remain outside the stomach (or other organ). The potential advantage is the use of the insulating properties of various membranes covering organs. Another potential advantage is the reduction of organ damage and / or invagination damage. Optionally, an envelope of the pancreas is removed or reduced, to help electrical conduction to the pancreas. One example electrode configuration is two sets of electrodes on the same side of the pancreas. For example, electrodes 620 and 624 or 610 and 612 can be applied between them to a field that will also cover part of the pancreas. Another example is the electrodes 634 paired with electrodes 630. In this last example, not only the electrodes on the same side of the pancreas, but also oriented in such a way that a significant portion of the field will not flow through the pancreas as well as any portion of the pancreas is directly between or slightly deviated from being directly between the electrodes.

Another configuration of the example electrode is on opposite sides of the pancreas. For example, the electrodes of set 630 (or 636) paired with the electrodes of sets 632. Optionally, a plurality of electrodes are selected from each set, to allow selective electrification of different portions of the pancreas. Another example is an electrode from set 636 and an electrode of 610-618 and / or the transverse colon (not shown). Another configuration of exemplary electrodes are separate electrodes of the pancreas, for example, electrodes 626 and 628. Another example electrode configuration is electrodes whose field will travel around an organ, for example the stomach. The stomach is hollow, and in this way in general a good insulator. An example is electrodes 636 (or 630-634) paired with electrode 626. Another configuration of electrodes of examples is as follows. Four electrodes are attached or placed on top of the pancreas, with alternative electrodes that shorten together, for example, on the left most electrodes are positive or negative. In an exemplary embodiment of the invention, the electrodes on the left side are 2-3 cm from a main part of the pancreas. The next three electrodes are 1-2 cm apart and. The last electrode is 6-7 cm from a tail of the pancreas. In an exemplary embodiment of the invention, the electrodes are needle electrodes suitable for laparoscopic implantation. In various implementations, a greater or lesser number of these alternating electrodes may be used in various orders of electrodes (for example, 2-1-2-1 - the numbers indicating the electrodes of the same polarities) may also be provided. In some orders, the number of different electrodes of different polarities is not the same. The distances between the electrodes do not need to be uniform. In particular, the electrodes do not need to depend on a straight line. Optionally, however, the electrodes are placed in an easy location to achieve the use of a minimally invasive technique.

CALIBRATION AND PROGRAMMING The pancreatic controller 102 can be implanted not only after a known stable disease state, but also during a current disease progression. Under these conditions and even in the steady state, the cells that have to be controlled by the controller 102 are expected to be sick and / or over-stressed and may behave somewhat unpredictably. Thus, in an exemplary embodiment of the invention, the optimization of pancreas control may require calibration of the controller after it is implanted. However, it should be noted that this calibration is not an essential feature of the invention and may even be superfluous, especially if a reasonable estimate of pancreatic physiological status can be determined prior to implantation. Figure 7 is a flow diagram of an exemplary method of implementing and programming a controller, according to an exemplary embodiment of the invention. You can also practice other methods. Before implantation, a patient is optionally diagnosed (502) and the benefit of implantation is optionally determined. However, it should be noted that the controller 102 can also be used for diagnostic purposes, due to its ability to take measurements for prolonged periods of time and to determine the response of the pancreas cells to different stimuli and situations. A controller is then implanted, for example, as described above, and an initial schedule (504) is provided. The initial programming can be done while the controller is outside the body. However, in an example embodiment of the invention, the controller is capable of extensive programming when it is inside the body, for example, as will be described below, to be able to control the selective application of one or more of the many different logic and pulse schemes, possibly differentiate one or more of the controlled zones. During a step of obtaining information (506) the behavior of the pancreas is traced, possibly without any active control of the pancreas. This information retrieval optionally continues throughout the controller's life. In an exemplary embodiment of the invention, the information obtained is reported periodically and / or continuously to a physician who is treating, for example, using an external unit 116. An example report is the levels of glucose in the body and the main events- that affect glucose levels. Alternatively, for a simple accumulation of information, information retrieval also uses sequences - for test control to determine the pancreatic response to various pulse shapes and sequences. In an exemplary embodiment of the invention, the step of obtaining information is used to determine the physiological pathologies and especially to detect one of the feedback mechanisms and / or direct feeding that are -damaged. These mechanisms are optionally supplemented, replaced or canceled by the controller 102. Alternatively or additionally, information collection is prepared to detect feedback interactions and direct feeding in the pancreas, especially the interactions between hormones, which possibly depend on the levels of glucose, hormone levels and / or history of stimulation. This information can be used to provide the parameters for a predetermined model of the pancreas. Alternatively, a new model can be generated, for example, using a neural network program. Possibly, several protocols are tested on control regions to determine their effect. The obtaining of information, and later the calibration and programming can be done on a per-person basis or even on a per-island or per-pancreatic basis. Optionally, baseline programming of other patients with similar disorders is determined. Optionally, various test sequences are timed to coincide with patient activities such as, for example, feeding, sleeping, exercise and insulin absorption. Also the controller's programming can be adapted to a sleep program, a program for food ingestion and / or other daily, weekly or otherwise known periodic activities. Possibly, the obtaining is improved with the test of hormonal levels and / or other physiological parameters for which - or not detectors can be provided on the pancreatic control. These measurements can be used to learn which glucose levels (or other parameter) physiological and / or level changes are caused by this hormonal level. In this way, normal and / or abnormal hormone levels can be determined later without a dedicated detector. Possibly, the additional detectors are offline, for example, laboratory blood test. Alternatively or additionally, an ambulatory monitor is provided to the patient, in which the patient enters diverse information. After a better representation of the. In the way that the pancreas is acting, a first reprogramming can be performed (508). This reprogramming can use any means known in the art such as, for example, magnetic fields and electromagnetic waves.

The reprogramming optionally implements the partial control of the pancreas, (510). This partial control can be used to avoid an over-tension of the total pancreas. Some of the controlled portions can be suppressed, for example, by using hyper-polarization pulses as described above. However, it should be noted that because pancreatic damage usually does not cause immediate life-threatening situations and because the pancreas is formed of a plurality of practically independent portions, there is considerably greater decline in the test of the effect of the pancreas. control sequences and even the long-term effects of these sequences, which exists in other organs such as the heart. In an optional step 512, the interaction of the pharmaceutical or hormonal treatment with the controller can be determined. In this context, it should be noted that electrophysiological, cardiac and nervous pharmacists may also be useful for the treatment of pancreatic disorders. Alternatively, pancreatic control may be convenient to neutralize the negative side effects of these ingested pharmaceuticals for non-metabolic disorders. Alternatively or additionally, the effect of the pharmaceutical products on the behavior of pancreatic cells and / or the feedback interactions is determined. The steps 508-512 can be repeated a plurality of times before adjustment to a final schedule 514. It should be noted that even this final schedule can be periodically re-evaluated (516) and then modified (518), for example, as the pancreas and / or the rest of the patient improves or degrades, or to apply various sequences- to control long-term effects. In an exemplary embodiment of the invention, a test for tissue viability of the controlled and / or uncontrolled portions of the pancreas is optionally performed periodically, for example, to assess the patient status,, to update the patient's initial values and to assess the effectiveness of the therapy. The sample methods of the viability test include analyzing the electrical activity, responses to changes in., Glucose level or insulin levels and / or responses to various types of electrical stimulation. In an exemplary embodiment of the invention, the programming, measurements and / or treatments tried above (possibly including pharmaceutical treatments) are stored in a memory portion of the controller 102. Alternatively or additionally, programming may include special sequences that take in account of digestion of pharmaceutical products. In an exemplary embodiment of the invention, when a patient ingests a pharmaceutical product or the insulin controller 102 is notified, for example by manually entering the external unit 116 or automatically by the administration method. If the patient does not take care of ingestion of pharmacists, insulin and / or glucose, a compensatory control sequence is provided, possibly regardless of whether the patient is provided with an alert or not.

EXPERIMENT In an exemplary experiment, a unipolar sieve electrode is placed under the pancreas of a pig and a needle electrode is inserted into the coating of the abdominal wall as a base. A current of pulses was applied (5 Hz, 5 mA, 5 ms duration) for five minutes and resulted in the decrease in serum glucose from 89 to 74 mg / dl. Serum insulin increased from 3.8 to 5.37, microU / ml, measured using the ELISA method. Both glucose levels and insulin levels returned to baseline after 30 minutes, in a different animal, the application for 5 minutes of a pulse of 3 Hz, 12 mA and 5 ms duration resulted in an increase of insulin from 8.74 microü / ml to 10.85 microU / ml. Figure 8A is a diagram showing the effect of this electrical stimulation on insulin levels in six animals. However, it should be noted that, clinically, the effect on insulin and glucose levels is not very large, depending on whether they are close to the initial values and remain close to the initial values and the change in insulin levels will have a physiological effect relatively small Figures 8B-8D are diagrams of an experiment in a pancreas ± n situ, showing an increase in insulin secretion, according to an exemplary embodiment of the invention. In this experiment, similar to the experiments in rat pancreas described below, a pulse of 5Hz, 5ms, bi-phasic was applied for one second of each minute. Figure 8B shows the measured electrical activity. The zone between 30 and 60 minutes is when the stimulation was applied. Figure 8C shows a significant increase in insulin during signal application, which indicates that in a practical system an increase of, for example, more than 20%, 40%, 60%, 80%, 100%, 200% or more can be achieved. Figure 8D shows the measurement during a control experiment without stimulation.

ADDITIONAL EXPERIMENTS Figure 9 is a diagram showing the effect of electrical stimulation on blood glucose levels, in an experiment in which glucose levels are increased faster than would be expected only by the addition of glucose. insulin secretion. In a sub-diagram 904 of diagram 900, glucose levels are reduced by the application of an SI stimulation pulse. In a sub-diagram 902 of diagram 900, the glucose levels are increased by the application of a stimulation pulse S2 and then reduced by the application of the SI pulse again. It is conjectured that the simple reduction of insulin secretion may not be sufficient to explain this rapid and large increase in glucose levels. Instead, glucagon secretion is causing a release of glucose from the liver, increasing the level of glucose in the blood. Diagram 900 comes from an experiment on a rat that was anesthetized with pentobarbitine (40 mg / 1 Kg). After fasting the rat was given a continuous infusion of 5% glucose at a rate of 2 cc / hr. During the experiment, the rat was ventilated with oxygen. What is shown in diagram 900 are the results of an analysis by means of a glucometer "Glucotrend", of Rosche, of • the blood coming from the right jugular vein every 5 minutes. SI and S2 have a similar form, except that S2 has an amplitude of 2 mA and a duration of 3.5 minutes, whereas SI has an amplitude of 1 mA and a duration of. 5 minutes The pulse includes an initial increase. For a delay of '150 ms and' a set of 7 increases in the utilization coefficient to 50% distributed over 400 ms. The total pulse was repeated every 10 seconds. The initial increase was 50 ms in duration. Both electrodes were iridium oxide coated with titanium. The geometry of the electrodes was of a winding, length of 8 mm, diameter of 1.2 mm, with a diameter 100 μ and a wire of 3 filaments. The roll was stuck on a pad. silicone (for isolation and prevention of mechanical damage.) Two of these electrodes were placed along the pancreas, one above and one below (when the rat was on its back.) Figures 10A-10B, 11A-11B, 12A -12B and 13A-13B are pairs of figures, each pair shows a diagram and a pulse diagram of additional experiments using an adjustment similar to that of Figure 9. In Figures 10, 12 and 13 both electrodes are above of the pancreas and the signal was applied for 5 minutes.

In Figure 11, both electrodes are below the pancreas and the signal was applied for 5 minutes.

ADDITIONAL EXPERIMENTS IN A PERFUNDED RAT PANCREAS A series of experiments was carried out on a perfused rat pancreas. The pancreas was actually disconnected from any control system (eg, blood, nerves), although it did not disconnect from its surrounding ligaments and organs. In an anesthetized rat, all of the main blood vessels were attached around the pancreas and a cannula was inserted into the descending aorta, the thoracic aorta was grasped and the circulation of surrogate blood (with glucose) was allowed through the celiac trunk. towards the liver, pancreas and duodenum. The perfusate is then collected from the vein cover for further examination. This does not aniguila the rat. In general, the rate of application once in a minute was selected because it generally coincides with the speed of the natural sudden increase of the pancreas. For example, some of the applied pulses have a bi-phasic waveform, 5Hz, a phase duration of 5 ms applied for 1 second every minute. In general, a variety of different frequencies were tested. In other creatures (for example, humans) and / or various conditions, this speed may be different. Glucose levels are generally controlled to be approximately 10 mM. Figure 14 is a diagram showing an experiment in which the application of stimulation pulses increases the amplitude of sudden increases although they do not induce new sudden increases. Due to the electrical nature of the measurements, the stimulation pulses appear as lines that cover the total vertical variation of the diagram. This in general is true also in the other diagrams. For clarity, (some) sudden increases are measured with the letter "B", and stimulation pulses with the letter "S". In this experiment, performed in situ, in the rat, as described above, the pulse was a balanced rectangular bi-phasic pulse at 5 Hz, a pulse of 10 ms in duration, a maximum amplitude of 10 mA, a duration of the application of 0.5 seconds and was applied every minute. This pulse evidently does not induce significant new surges when applied to a time without sudden increase and increases the amplitude of the sudden increases that occur and / or during or after the pulse. Possibly, there will be a sudden increase during the course and it is not detected due to the limitations of the measurement system. In addition, the speed of the repeated increments did not seem to change, however, it is believed that using other parameters, the speed of the sudden increase can be controlled electrically, without using only a direct advance. It should be noted that the diagrams showing the electrical activity are only static and do not show all the fine details of the electrical signal measurements, due to the resolution limitations of the layout and presentation process. Figure 18B shows a measurement of insulin levels (shown in this and other diagrams in units of micro-units per milliliter). The stimulation evidently caused a corresponding increase in the level of insulin. However, in the first of two stimulations, the level evidently did not increase immediately or during the stimulation, but only towards the end or after the end of the pulse. It is conjectured, that a pulse may have two effects on beta cells, one for priming them for insulin secretion (for example, promoter generation) and one for initiating or suspending secretion. It is conjectured (and how it will be supported by other results) • 5 - • experimentally later) that larger pulses may have the effect of preventing insulin secretion, possibly by hyper-polarization of beta cells. Depending on the degree of hyper-polarization and the amount of insulin generated in the cells and / or possibly on the environmental inputs (for example, the glucose level and / or the hormonal level), a cell can be stimulated to secrete even during an application of the electric field may be free to secrete after the field is removed, or secretion may be prevented for a duration after the field is removed. If the stimulations are closed, the cell can be prevented from secreting until the stimulation series is completed or until its internal activities are strong enough (for example, stimulated by the internal storage of insulin) to overcome the hyper-polarization. In this and other observed effects, it should be noted that while various mechanisms have been conjectured, the effects discovered in some embodiments of the invention can be used even without a correct understanding of the biochemical and electro-physiological processes behind them. In this way, pulses that have lengths between 1 and 40 ms can have significantly different physiological effects. This may suggest that the use of pulses of lengths 0.5, 1, 2, 5, 10, 15, 20, 32 and 40 ms or pulses of shorter, intermediate or longer duration to achieve various effects. An alternative interpretation is that frequency affects the behavior of beta cells.

In this way, they can be used up to various frequencies, such as, for example, 2 Hz, 5 Hz, 10 Hz, 15 Hz, 20 Hz or lower, intermediate or higher frequencies. A composite, alternative interpretation is that the combination of pulse duration (for example, one or both of the duration of each sub-pulse, measured in milliseconds in some examples and the length of each set, measured in total seconds and fractions of them in some examples) and the frequency dictates an approximate total of stimulation, this total stimulation can determine the effect of the pulse, at least for some variations of frequencies and amplitudes. Figures 15A-15C are diagrams and two magnifications thereof - of an experiment showing that a stimulation pulse synchronizes the repeated increase activity, possibly without the immediate generation of a new sudden increase. The experiment was carried out in situ, according to the above, with stimulation parameters that define a rectangular bi-phasic eguilibrate pulse at 10 mA, 40 ms at 20 Hz, applied for 500 ms. The ". -. .... 161. - - • Figures 15B and 15C show increases of two stimulation pulses, which show that none of the immediate sudden increases were obviously generated (unless they are very short and are masked by the stimulation). Possibly if the speed of stimulation was considerably slower, the sudden increases that occur naturally could occur. In an exemplary embodiment of the invention, the speed of the sudden increase is controlled (for example, it becomes greater or less than the natural) to some degree by applying this type of pulse. Figures 16A-16C are a diagram and two enlargements thereof of an experiment showing a new induction of sudden increases by a stimulation pulse. The effect of the new repeated increase is practically immediate. As noted above, it is conjectured that the duration of the stimulation pulse is what determines whether there will be a delay before a sudden increase occurs and / or the degree of this delay. One possible support for this is that no second increment repeated after approximately 5 seconds is shown in Figure 16, which leads to the belief that this type of pulse stimulates the creation of a sudden individual increase., at a variable delay and / or can be used to delay the onset of the naturally occurring sudden increase. In any case, once the repeated increase occurs, natural mechanisms, such as, for example, re-polarization and exhaustion can prevent a next repeated increase from occurring too early. Figure 17 is u? diagram of an experiment that shows that a stimulation in the middle part of a sudden increase will not stop the repeated increase, in some embodiments of the invention. The sudden increase of the left side is shown by comparison, in such a way that the effect of the pulse on the sudden increase (for example, on the duration) can be observed. The effect on duration and amplitude is unclear and may be insignificant or may be significant for duration and / or amplitude. As noted above, Figure 14 shows an increase in amplitude as a result of this stimulation. The pulse parameters are 10 mA, 2 ms, at 20 Hz, for 500 ms, applied every 1 minute. Figures 18A and 18B are diagrams showing the changes in insulin level evidently caused by the stimulation. Figure 18B was discussed above. Figure 18A shows two sets of duplicate measurements, made on the same samples, to ensure the accuracy of the insulin measurement. As can be seen, the insulin levels increase during or after the stimulation in relation to the stimulation. It is believed that the increase in insulin level may be a delayed effect of stimulation that causes a generally increased activity of the beta cells, as well as possibly also a momentary increase in production. The stimulation (using these pulse parameters) evidently causes the improvement in the values of insulin that can be retarded. Possibly, the stimulation itself will not allow an increase, even though the effect of the stimulation is that of an increase. The samples were produced with three minutes of separation. The pulse parameters were 10 mA, 10 ms, at 20 Hz, for 500 ms, repeated every 1 minute. By reference, Figure 19 is a diagram showing the relatively constant initial values of insulin levels in a perfused rat pancreas, without stimulation.

ADDITIONAL EXPERIMENTS IN MINI-PIGS IN LIFE For these experiments two mini-pigs (called Venus and Shifra) were used. The pigs, weighing between 35 and 40 kg, had electrodes implanted in their pancreas. Four or six electrodes were implanted, however, only four were used, with two electrodes implanted at each end of the pancreas and shortened. The electrodes were wired electrodes separated 2 cm inside the pair and inserted at a depth of 3-5 mm, this length will be electrically driven. The pigs were deprived of food and then fed either pig feed or cubes of sugar (sucrose) to eat. The experiments were repeated for the same animal with and without stimulation, as will be described later. The pigs remained alive and apparently unharmed by experimentation, which occurred over a period of several months. Figure 20A is a diagram showing the changes in insulin levels with and without stimulation, in a live mini-pig that ingested sugar cubes (30 cubes of 2.5 grams of sucrose each, eaten in a few minutes), after the deprivation of food. A follow-up experiment showed no significant differences between feeding with sucrose and feeding with glucose, which will be a technically more difficult fluid to feed for a pig. Two series of stimulation were applied, one with a duration of 15 minutes and the second with a duration of 10 minutes. Zero time is the start of feeding. The pulse was 100 Hz, 10 ms, 1 second in duration, every minute, the amplitude is 5 mA. As shown, the insulin increase in the stimulation experiment was faster and greater than without the stimulation. Possibly this is an improvement effect by means of which insulin activity (pancreas response) is amplified by stimulation. Figure 20B is a diagram corresponding to diagram 20A, showing the stimulation case of the relationship between glucose level and insulin level. As noted above, and in the analysis of Figure 21A, there are physiological mechanisms, such as, for example, the secretion of glucagon which increases glucose secretion if the insulin level is high. In some embodiments of the invention, a minor stimulation may be applied to reduce this glucose secretion. Figure 20C is a diagram corresponding to diagram 20A, showing the cases without stimulation, the relationship between glucose level and insulin. Figure '21A is a diagram showing the changes in insulin levels with and without stimulation, in a live mini-pig that was fed, approximately 700 grams, after the feed deprivation. It should be noted that the provision of 16.6 Food in general is controlled less than the sugar supply. Two series of stimulation were applied, one with a duration of 15 minutes and the second with a duration of 10 minutes. Zero time is the start of feeding. The pulse was 100 Hz, 10 ms, duration of 1 second, every minute, the amplitude is 5mA. The effect on insulin levels is • significant after the first stimulation, even after the second, possibly due to pancreas depletion or due to low glucose levels (shown in Figure 20B). It is conjectured that the pulse, as applied, does not arbitrarily cause the secretion of insulin, although it amplifies or primes the existing physiological mechanisms. In this way, stimulation when glucose levels are low does not necessarily cause an increase in insulin levels at high levels (which could be harmful in this situation). This can be a direct property of the pulse or it can be caused by various physiological mechanisms. Another possible, interpretation is that he had an observation that was continuous, the increase in insulin levels observed after the second stimulation could be continued. The relative delay and / or reduced speed of this increase may be due to one or more of the mechanisms described above. Figure 21B is a diagram corresponding to the diagram 21A, which shows blood glucose levels. While the blood glucose increased after the first stimulation, this increased less than the control situations and shortly after the maximum. This suggests that the pulse may have glucose levels directly or indirectly affected, a possible mechanism is that insulin secretion1 causes the secretion of glucagon or that glucagon secretion was induced directly by the pulse. Possibly, these effects are more pronounced if the insulin is produced as a bolus, in such a way that the insulin levels are constituted considerably and / or fast in the pancreas and / or in the body. Previous experiments clearly show that the application of electric fields can affect the behavior of the pancreas, for example, by increasing or decreasing the production of insulin with or without creating new surges, and that different pulses can have different behaviors.

ADDITIONAL EXPERIMENTS IN LIVING MINI-PIGS In the following experiments on living mini-pigs, the following protocol was used. A pair of electrodes were implanted in the pancreas of female Sinclair mini-pigs, adults. After they were given two weeks to recover from surgery, two types of protocols were performed. In a control protocol, 3 blood samples were taken while the pig was fasting. At time 0, a glucose load of 75 g was orally administered. Both samples were extracted every 5 minutes for a total of approximately 100 minutes. The stimulation protocols were the same as the control protocols except that a stimulation was applied immediately after the ingestion of the glucose. The pulse parameters were: bi-phasic waveform of 5 ms each pulse applied every 200 ms (5Hz). The amplitude was 6-10 mA. The duration of the stimulation was 15 minutes in this and the following experiments. Figure 22A is a diagram showing a delay in the maximum glucose and the reduction in glucose levels under stimulation conditions in a series of experiments in a first pig, according to an exemplary embodiment of the invention. The values of both control and stimulation are averages of 9 days each. It should be noted that the maximum glucose was both reduced and delayed by 20 minutes and also distributed over time. Some of these experiments can also be factorized in the diagrams of Figures 35A and 35B.

Figure 22B is a diagram showing a delay in the maximum insulin and reduction in insulin levels in some of the experiments in Figure 22A. These results are provided during 6 days of control and 7 days of stimulation. It should be noted that the insulin levels were apparently reduced from the entire digestion time, depending on the total insulin levels and the maximum size (although the maximum height was possibly not substantially reduced). This suggests that a factor without insulin is reducing glucose levels. The reduction of both glucose levels and insulin levels is expected to reduce the pressure on the pancreas for some disease conditions, for example, by reducing overstimulation induced by pancreatic disease. It should be noted that the delay and / or reduction in the maximum glucose may be sufficient to allow a patient to be freed from the need for a pharmaceutical or insulin intervention. Alternatively or additionally, by distributing the maximum, a patient may be able to ingest (only) slowly absorbed insulin instead of rapidly absorbed insulin, thus possibly simplifying the treatment protocol and / or the prevention of associated hypoglycemic events with a rapid absorption of insulin.

In addition, by reducing these maxima, less damage is caused to the patient's body systems from excessive levels of insulin and / or glucose. Alternatively or additionally, glucose monitoring can be performed less frequently, such as, for example, once a day or even less frequently, instead of several times a day. In an exemplary embodiment of the invention, a treatment protocol comprises reducing and / or delaying glucose maxima and concurrent slow-acting treatment, such as, for example, a daily modulation of "slow" insulin or suitable pharmaceutical products. As can be seen, even after the series of stimulation pulses is stopped, the glucose and insulin levels are not as high as the control situation. This may be a direct effect of the stimulation or it may be an indirect effect, for example, due to the reduction in the rate of glucose exchange. As shown below, in experiments with humans, prolonged stimulation times will be applied. It should be appreciated that, as noted above, in some treatment protocols, this may be convenient to stop stimulation during glucose digestion, for example, to observe the pancreatic response and / or allow it to rest.

Figure 23 is a diagram showing a reduction in glucose levels under the same stimulation conditions of Figure 22 in a series of experiments in a second pig, according to an exemplary embodiment of the invention. These results are an average of 3 days of control and 4 days of stimulation. Figure 24 is a diagram showing a reduction in glucose levels under the same stimulation conditions of Figures 22 and 23, in a series of experiments on a third pig, according to an example embodiment of the invention. invention. The results are the average of 5 days of control and 12 days of stimulation. Figure 22C is a diagram showing the reduction of glucagon as a result of the application of a series of stimulation pulses, according to an exemplary embodiment of the invention. The results of the stimulation are an average of three studies and a control study is used, all selected from the experiments in Figure 22 for which glucagon levels were measured. It should be noted that the glucagon reduction is mainly related to the an initial value, where the normal behavior is that the glucagon increases when they do insulin and 1? 2 glucose. However, some absolute reduction in glucagon is evident, although it may not be statistically significant. The reduction in glucagon secretion appears to continue for a considerable time after the stimulation is stopped. The reduction of glucagon secretion prevents the liver from adding glucose levels. While this result may indicate direct control of glucagon levels using electrical stimulation, an alternative explanation is that increased levels of somatostatin reduced both insulin and glucagon. Another possible explanation is that alpha cells, which secrete glucagon were desensitized. Another possible explanation is that the control of glucagon was indirect by the control of insulin (which by itself, it was observed, can indirectly be a result of the control of glucose levels via a mechanism without insulin). Figure 25 is a diagram illustrating that stimulation of glucose reduction according to an exemplary embodiment of the invention, operating under hyperglycemic IV fixation conditions, during an individual experiment. It should be noted that the reduction in glucose levels was only at the initial value levels and not lower. In this experiment, a pig was fixed at high glucose levels using a dextrose IV, using an initial 50% dextrose bolus of approximately 20-25 cc and then a constant infusion of 70-90 ml / hour for the duration of the experiment, including the recovery of glucose values. The experiment was started after the glucose levels stabilized. The duration of the stimulation was 15 minutes. As shown, the glucose level was recovered after approximately 20 minutes. Figure 26 is a diagram showing a lack of a damaging effect of stimulation according to an example embodiment of the invention, on normal glucose levels. An average of 2 days of control and 4 days of stimulation are shown. As previously noted, this can be used as a basis for the design of open cycle protocols in which it is not considered a possible over-stimulation that would be harmful (although possibly a waste of energy). In a further experiment, two pigs were continuously stimulated for 24 hours a day for two weeks, using the series of pulses 5Hz, 5ms, bi-phase, 5mA and no adverse reactions were seen on the effects of pancreatic function or histology. pancreatic In particular, no effect on the exocrine functions could be observed as changes in feces.

RESULTS OF EXPERIMENTS ON A HUMAN BEING A series of experiments was carried out on a human volunteer patient. The patient is a 45-year-old woman with a one-year history of type II diabetes. The patient was of Hindu extraction, with a weight of 71 Kg, 1/61 meters high and treated with Gliclazide 80 mg and Metformin 500 mg twice a day. The patient underwent abdominal surgery to remove the gallbladder. Before surgery, the patient had a fasting insulin level of 11.1 microunits per ml, a fasting C-peptide level of 2 ng / ml and a HbAlC of 5.8-s. For the removal of the gallbladder, a laparotomy was performed in the middle part. Then the smaller sac was opened through the gastro-colic omentum. The stomach and intestines were retracted respectively allowing the exposure of approximately 7 x 5 cm of the pancreas. Four wires were inserted for commercial stainless steel temporary cardiac placement manufactured by A & amp; amp;; E for the pancreatic, one pair or one end and one pair over the other. Two leads were also joined for the pancreatic record, one between the two electrodes on one side of the pancreas and closer to one electrode and the other that registers the derivation between the two PST electrodes. The electrodes were channeled to a 7 Fr JP abdominal drainage housing, an electronic circuit and a fixed suture to the pseudocapsule of the pancreas. The electrodes and drainage were guided and extracted through the left abdominal wall. A second drain of negative pressure was placed near the pancreas and guided to the right abdominal wall, the electrode joining procedure took 1.25 hours. The amylase values were 127.5 U / L on the first day and ~ 30 U / L on the next day, indicating a good recovery. Gl mobility was recovered on the first day and no fever was experienced during and after the experimental period. On the sixth day after surgery, the electrodes were removed, without anything happening. Several series of stimulation and measurement were conducted during the few days after surgery. No side effects of any kind were reported after placement, stimulation and removal of the electrodes. Two types of protocols were conducted. A control protocol and a stimulation protocol. In the control protocol, 3 blood samples were taken while the patient was fasting. At time 0, a glucose load of 75 g was orally administered. Blood samples were collected for a period of three hours after the administration of glucose. A control experiment was conducted on the morning of the surgery, before conducting the implantation, another was conducted one day after the surgery. The stimulation protocol was similar to the control protocol except that this electrical stimulation was provided, which had the parameters of (5 Hz, 5 ms, bi-phasic 5 mA) with or after glucose. The stimulation protocols were performed on the second and fourth days after surgery. Figure 27 is a diagram showing the effect, in a human being, on glucose levels, of a stimulation according to an exemplary embodiment of the invention. As with mini-pigs, glucose maxima were reduced and / or delayed. Figure 28 is a diagram showing the effect on insulin levels of the experiments in Figure 27. Insulin levels were not measured in the first control case, although they were measured in the others, as shown. The maximum insulin values were reduced and clearly delayed compared to the control situation. Figure 29 is a diagram showing the effect on the C-peptide levels of some of the experiments in Figure 27. The C-peptide values were reduced and the maximum was apparently retarded. These measurements were carried out only in a control protocol and a stimulation protocol. This measurement was used to validate insulin measurements. Figures 30A and 30B show the effect of electrical stimulation during fasting on glucose levels, on two different occasions during day five of the convalescence period of Figure 27. No substantial reduction in glucose levels was observed. . Figures 31A and 31B, which correspond to the Figures 30A and 30B show the effect of electrical stimulation during fasting on insulin levels. No substantial change in insulin level was observed, except possibly during a small increase in insulin level, which appears to be a return to baseline. The fall of pre-stimulation can be caused by the apprehension of the patient, in any case, if this fall is ignored, it is observed that the insulin levels remain relatively constant before, during and after the stimulation. Also, insulin levels remained low (for example, below 20) every time.

REDUCTION OF INSULIN AND GLUCOSE IN ANIMALS Figures 32A and 32B are diagrams showing the reduction of glucose and insulin in a pig, according to an exemplary embodiment of the invention. Figures 32C and 32D show accumulated levels of glucose and insulin in the pig of Figures 32A and 32B. A pig (that is, of the type of the Figures 22ff) was fed an oral glucose amount of 75 grams of glucose mixed with 14 grams of fish gelatin and 1 cup of water. The feeding time was approximately 2-3 minutes, starting at time 0. The horizontal line in the figure shows the time of application of a pulse that had the parameters, as previously used, of a bi-phasic pulse that had a positive 5 msec section immediately after a negative 5 msec, applied once every 200 msec (for example, a delay of 190 msec between electrifications), and continued for 1 hour. Glucose was measured using an Acucheck glucometer, using blood from a jugular vein that was removed once every 5 or 10 minutes during the determination of both glucose and insulin levels. The insulin level was measured using a radio-immuno-assay. In general, the same experimental parameters were used for all pigs, except where it was observed otherwise, for example, that the durations varied. Except where otherwise noted, the stimulation device was implanted. The following electrode was used: a joined line electrode having a length of, for example, 15-22 mm was used. The following bonding procedure was used. A needle (curved for the pancreas) and carrying a nylon 00 string was pushed through the tissue and through a 'small' silicone pad. The electrode was pushed along the throat in such a way that it remained mainly in the tissue. The silicone pad was attached to the tissue using a standard surgical fastener. The nearest portion of the electrode had mounted on it a small silicone pad with holes for suturing the tissue (only performed in the stomach). The electrode itself is a platinum-iridium electrode coated with titanium nitride, to increase its capacitance and thereby allow larger fields to be applied. Other electrodes can also be used. As can be seen in Figure 32A, the glucose level was reduced (and some of the maximum was delayed) in a stimulated case (7 average repetitions) in relation to a maximum control (8 average repetitions). As can be seen in Figure 32B, the insulin maximum was both reduced and delayed. The time integral of insulin levels and glucose levels through the first 30 minutes was also significantly reduced, as shown in Figures 32C and 32D. The time integral is simply the area under the curve between the observed times (for example, 0 and 60 minutes). Figures 33A-33D show similar results for another pig, with 8 control experiments and 4 stimulation experiments. In this case, the maximum insulin was not reduced in height, but only in width. Figure 34 shows accumulated levels of glucose under various conditions of application in the field (control, 15 minute signal and 60 minute signal), according to example embodiments of the invention. In particular, the response to the dose is more significant for longer times, Figures 35A-35D are diagrams showing the reduction of glucose and insulin in another pig, according to an example embodiment of the invention, in which the device it was joined externally via temporary placement electrodes (AEI) to the pancreas. The stimulus was applied for 15 minutes only. A delay in the maximum insulin and glucose, as well as a reduction in the total amount, could be observed. Figures 35C and 35D show the accumulation through 15 minutes only. Seven control and 5 stimulation experiments were carried out.

Figures 35A and 35B may include the experimental results which were also used in Figures 22A and 22B. Figure 36 shows the reduction of the glucose level in another pig, according to an example modality of the invention in the field a stimulus was applied for 15 minutes, using an external stimulator (and internal electrodes). A reduction in the maximum and total glucose levels was observed. In addition, the response to glucose does not appear to be delayed. It was observed that in some disease situations, it is convenient to delay this glucose maximum. In other situations of illness it is convenient to maintain the timing of the response but reduce its amplitude. In some situations of illness, simply truncating the response to a certain amplitude is a convenient effect. There were 11 control experiments and 9 stimulation experiments. Figures 37A and 37B are diagrams showing the reduction of glucose and insulin in a dog, according to an exemplary embodiment of the invention. A stimulus was applied for 60 minutes to a right lobe of a dog's pancreas, a repeat. As can be seen, the glucose maximums and insulin maxima were reduced although they were not significantly delayed. The pulse applied was the same as for the pigs. Glucose was injected via a tube into the stomach and was given at 1.5 grams per kilogram of body weight. While perhaps it was not statistically significant, the response of the dogs seemed to be close to the response of the human being with respect to the truncation of the maxima in comparison with the delay and truncation. Possibly this varies between people and / or disease states. Figures 38A and 38B are diagrams showing the reduction of glucose in two dogs where electrodes were placed in a stomach, according to an exemplary embodiment of the invention. There were 6 repetitions of control and 5 repetitions of stimulation, for the first dog and 7 and 6, for the second dog. It was shown that the glucose maxima were reduced, possibly providing an effect of a truncated maximum, rather than a delayed and / or narrowed maximum. In Figure 38A, the field was applied to both the posterior and anterior walls of the stomach, simultaneously, with two electrodes on each side. In Figure 38B, a signal was applied only to the anterior wall. The field was the same sequence that was used for the pigs and was synchronized for a sensitization of the electric field in the antrum.

In each "case of local sensitization" (eg ~ 10 seconds) a second stimulation sequence was applied. Figure 38C shows a series of four experiments in dogs, in which a signal was applied, as well as that which was used in pigs only for the posterior side of the stomach. Six control experiments and four stimulation experiments were carried out. The stimulation experiments were divided into two pairs. A first pair, in which the glucose reduction was greater and a second pair in which the glucose reduction was less pronounced. In the experiments with a more pronounced reduction in glucose, the stimulation signal was applied in each different sensitized "local case". In the experiments with a less pronounced reduction, the signal was applied in each "local event". It is conjectured that a less frequent excitation may allow a recovery of the mechanism that is in operation, thereby allowing a greater effect to be achieved without an associated adaptation. In particular embodiments of the invention, the application may be less frequent, for example at a ratio of 1: 5, .1: 10 or less, or more frequent, for example at a ratio of 1: 1.5 or more. Alternatively or additionally, the duration may be shorter than 4 seconds, for example, it may be 1 second or 2 seconds, or it may be longer, for example, 6 or 10. Other intermediate numbers are also possible. By reference, Figure 38D shows an online diagram of the pancreas (right lobe) and the stomach of a dog. FIGS. 39A and 39B are diagrams showing the reduction of glucose in two dogs where the electrodes were placed in a stomach, according to an exemplary embodiment of the invention. This is described in the provisional • application of the United States, 60 / 488,964, filed on July 21, 2003, the disclosure of which is incorporated herein by reference. Reference is made to Figure 39A which is a graph showing measurements of blood glucose levels taken during experiments performed in accordance with one embodiment of the present invention. A single dog was anesthetized, and 2 electrodes were implanted in an anterior external wall of the dog's antrum, between approximately 2 cm and approximately 3 cm from the pylorus. The electrodes were conducted to apply an electrical signal with a square-wave shape that had 100 bi-phasic pulses, each phase of each pulse had an amplitude of 8 mA and a duration of -. •• i .., -. 6 ms The waveform was applied after the detection of the appearance of each slow wave of the dog's stomach (approximately 4 to 5 times per minute). While this is one. sequence of pulses different from the others used in the experiments of the present, it should be noted that there is some similarity between the sequences, explaining with this -possibly 'the effect. The measurements were taken in two separate days, approximately at the same time on each day, after a twelve-hour fast, while the dog was conscious. An electrical signal was applied on one of these days, and the other day it served as a control. On each of the days, glucose consumption, by injection into the snout, started at time 0 and continued for approximately two minutes. The electrical signal was applied starting at time 0 and continuing for approximately 15 minutes. • The measurements were taken using the same glucose meter on both days, and a validation of each measurement was performed using two different sets of measuring equipment. A dotted line and a solid line show the measurements taken on the control day and the day of the signal application, respectively. As can be seen, the application of the electrical signal resulted in a substantial reduction in the level of 'V •' 186, r. blood glucose and all points during the measurement period. Referring to Figure 39B, which is a graph showing measurements of blood glucose levels taken during experiments performed in accordance with one embodiment of the present invention. A second dog, different from the dog described with reference to Figure 39A, was anesthetized, and 2 electrodes were implanted in an external anterior wall of the dog's antrum. The electrodes were implanted between approximately 2 cm and approximately 3 cm from the pylorus. An electrical signal similar to that described with reference to Figure 39A was applied, and the same 5 experimental protocols were followed. In the experiment whose result is shown in Figure 39B, however, the electrical signal was applied for approximately 20 minutes. A dotted line and a solid line show the measurements taken on the control day and on the 10th day of the signal application, respectively. As can be seen, the application of the electrical signal resulted in a substantial reduction of the blood glucose level during the measurement period.

ANALYSIS The above results indicate that the control of glucose levels in a person may possibly be, at least in part, without a significant increase in insulin levels and even decrease these levels. While a physiological model is not necessary for the application of these results, several pulses application logics can be formulated along with certain models. It should also be noted that each of these models can explain only part of the effect with the full effect which is the result of a combination of different physiological trajectories and effects. One possible explanation for the effects of pulses for insulin and glucose reduction is that one or more non-insulin hormones, for example, GLP1 or other Gl hormones, known or unknown, are released and that "these hormones affect absorption. of glucose or glucose secretion Possibly, these hormones act directly on the body cells or on the hypothalamus.These hormones can increase the efficiency of insulin or the sensitivity in various peripheral cells on the brain.Alternatively or additionally, the secretion of glucagon or a different hormone that affects 1§8 the secretion of glucose. In addition to the direct electrical stimulation of the cells involved in hormone secretion in the pancreas, there are other possibilities. Possibly, the electrical stimulation changed the patterns of blood flow in the pancreas, as described above, to have an effect. Another 'explanation is that the electrical stimulation affected the levels of adipose tissue in the pancreas itself. Another possible explanation is that the electrical stimulation affected the neural trajectories in the pancreas and / or the liver. Possibly these neural trajectories control the secretion of glucagon or activate glucose transporters that do not depend on insulin in cells of remote tissue. For example, it is shown that the implanted islets have an incorrect glucagon secretion. This is possibly due to a loss of nerve connections. The nerves that are stimulated, for example, can be nerves that cause secretion and / or prevent secretion. Alternatively or additionally, the nerves may be, for example, nerves that are sensitive to pancreatic, glycemic and / or hormonal activities. Alternatively or additionally, the connections of the separation of the nerves and / or other excitable pancreatic tissue can be affected. It should be noted that for some nervous tissue type effects, the percentage of simulated pancreas may be less important due to the propagation of stimulation effect by the propagation of nerve signals in the pancreas and / or outside the pancreas. One possible explanation that includes nerves is that the electric field affects the nerves in or near the pancreas either directly or indirectly. Possibly, these nerves release materials that affect the muscles, brain or other organs. Possibly, the nerves directly affect the brain which then causes the release of these materials. Alternatively or additionally, nerves affect other tissues for the release of these materials, possibly via ganglionic connections. After a partial list of signaling guiding products whose secretion may be affected (eg, increased and / or decreased) by the effects of stimulation: Nitric e, ATP, Adenosine, Dopamine, Norepinephrine, Acetylcholine, Serotonin (5- HT), GABA, Glutamate, Aspartate, Glycine, Histamine, Angiotensins, Bombesin, Bradikinina calcitonin, Peptide carnosite related to the calcitonin gene, Cholecystokinin corticotropin, Corticotropin-releasing hormone, Delta-inducing peptide, FMRFa'mide Galanin, Polypeptide inhibitor gastric peptide, gastrin release peptide, glucagon gastritis, MSH gonaddrelin, MSH libration inhibitory hormone, MSH-releasing hormone, neuropeptide Y motility, neurotensin neuropisins, opioid-endorphin peptides, pancreatic polypeptide, hormone-releasing hormone inhibitor hormones Pituitary pituitary peptide, pituitary hormone-releasing hormones, Hormone for the p inhibition of release of prolactin, hormone for the release of prolactin, Protirelin, secretin Somatomedins, Somatostatin-releasing hormone somatotropin, Taquikinin Vasoactive Intestine, Peptide, Vasopressins, orexin, insulin and / or substance P, and / or any other products known or unknown signaling chemicals. Another possible explanation is that the electrical stimulation affected other organs in the abdominal cavity, such as, for example, the liver, the stomach or possibly the fat cells in the Omentum and caused them to change their activity and / or secrete hormones. In any case, the placement of electrodes in the pancreas, at either end, had this desired effect, both in pigs and in humans. It should be noted that a practical device may include one or more detectors, for use in laboratory or functional settings, these sensors indicate whether a pulse is having one of the effects described above (eg, on glucagon secretion, or glucose). , or the absorption of glucose and / or nervous tissue) and help with this in the programming and / or control of the pancreatic controller 102.

EXAMPLE APPLICATIONS The above pancreatic controller 102 can be used after a diabetic state is identified. However, optionally, the controller is used for a better diagnosis and involves a disease state and / or to prevent a final diabetic state from being present, for example, by supporting the pancreas. In this way, a temporary device mode is optionally additionally provided for a permanently implanted device. In another application, strict control of body insulin production and blood glucose levels are used not only to prevent an obese patient from developing diabetes by overworking the pancreas, but also, (simultaneously or alternatively) to reduce body weight This scheme may require a strict prevention of high blood glucose levels, to avoid damage to the body. However, it is expected that by reducing the production of insulin "normal" glucose levels, feelings of hunger can be suppressed, as well as reducing the increase in adipose tissue mass. In an exemplary embodiment of the invention, the controller 102 is an independent device. However, a dual organic controller may be useful in some disease states. In one example, it is noted that many patients with pancreatic disorders also have heart problems. In this way, a combined cardiac / pancreatic controller may be provided, possibly sharing one or more of the wrapping / programming, power supply and control circuitry means. In another example, a controller for the uterus and a pancreatic can be combined to protect against pregnancy-related diabetes and inappropriate uterine concentrations. Another example dual organic controller is used for both the stomach and the pancreas. This controller is useful for obese people, to suppress stomach contractions and avoid feelings of hunger. In the same tissue, the level of insulin can be controlled to avoid hunger, or, in diabetic patients, to avoid hyper- or hypo-glycemia. In addition, as noted above, the delay of gastric emptying can also be used to delay glucose uptake, leading to a delay and / or reduction in insulin maximum. This delay can be used in addition to or instead of direct pancreatic stimulation, in some embodiments of the invention. In an example embodiment of the invention, the same electrodes are used for the electrification of the pancreas and the stomach, thereby providing both obesity control and glucose control with the same set of electrodes. It should be noted that reducing the load can also reduce the glucose load. These multipurpose electrodes can be placed, for example, on the pancreas, on the stomach or between the pancreas and the stomach. The placement of electrodes on the abdominal wall and / or the stomach and / or other internal organs may also be useful for non-pancreatic stimulation, for example, if the organ to be stimulated is relatively sensitive to the attachment of electrodes and / or relatively difficult to achieve by a desired method of surgery. It will be appreciated that the methods described above for controlling a pancreas can be varied in many ways, including, the change in the order of the steps, the steps are performed more frequently and less frequently, the arrangement of the electrodes, the type and order of applied pulses and / or the sequence: -particular and logical schemes used. In addition, the location of the various elements can be exchanged, without exceeding the spirit of the exhibition, for example, the location of the energy source. In addition, a multiplicity of diverse characteristics, both of the method and of the devices, has been described. It should be appreciated that different characteristics can be combined in different ways. In particular, not all of the features shown above in a particular embodiment are necessary in each similar example embodiment of the invention. In addition, combinations of the above features are also considered to be within the scope of some of the exemplary embodiments of the invention. In addition, some of the features of the invention described herein may be adapted for use with prior art devices, in accordance with other exemplary embodiments of the invention. invention. In addition, they include various means for carrying out the functions described above in the scope of the invention, for example, electrification means, means for generating pulses and / or means for sensitization. These particular geometric shapes used to illustrate the invention should not be considered as limiting the invention in its broad aspect to only those forms, for example, where a sphere electrode is shown, in other embodiments an ellipsoidal electrode. Some limitations are described only as limitations of the method and apparatus, the scope of the invention also includes the apparatuses programmed and / or designed to carry out the methods, for example, using a software or software program and the methods for electrify the device so that the device has the desired function. Also within the scope of the invention are surgical equipment that includes sets of medical devices suitable for the implantation of a controller and this controller. The titles of the sections are provided solely to assist in the navigation of the application and should not necessarily be considered as limiting, the contents described in a certain section, for that section. Measurements are provided that serve only as example measurements for particular cases, the exact measurements applied will vary depending on the application. When used in the following claims, the terms "comprises", "comprising", "includes", "including" or similar means "including but not limited to". It will be appreciated by one skilled in the art that the present invention is not limited to what has been described up to this point. Instead, the scope of the present invention is limited only by the following claims.

Claims

NOVELTY OF THE INVENTION Having described the present invention, it is considered as a novelty and, therefore, the content of the following CLAIMS is claimed as property: 1. A method for controlling the level of glucose, characterized. because it comprises: providing at least one electrode adapted to apply an electric field to at least one pancreas; and applying an electric field to the pancreas using at least one electrode, in such a way that the blood glucose levels are significantly reduced and the blood insulin levels do not increase significantly compared to a response to regular insulin in the same person. The method according to claim 1, characterized in that it comprises subsequently applying a second electric field to the pancreas, the second field increases the insulin levels. 3. The method according to claim 1, characterized in that the electric field is functional to reduce the secretion of glucagon. 4. A method according to claim 1, characterized in that the electric field is functional to reduce the secretion of glucose by a liver. .. •. -. The method according to claim 1, characterized in that the electric field is functional to increase the absorption of the thing by the cells in a body containing the pancreas. The method according to claim 1, characterized in that the electrical field is functional to affect the nervous tissue in the pancreas 7. The method according to claim 1, characterized in that the electric field is not exciter since it does not induce practically new repeated increments. of the activity of the islet in the pancreas 8. The method according to claim 1, characterized in that the electric field is applied as a variable field in bi-phasic balanced time and charge 9. The method according to claim 8, characterized because the electric field is applied for a short duration each period of time 10. The method according to claim 9, characterized by the period of time provides an application frequency between 1 Hz and 15 Hz. The method according to claim 9, characterized in that the period of time provides an application frequency of about 5 Hz. The method according to claim 9, characterized in that the duration is less than 30 ms. 13. The method according to claim 9, characterized by the duration is approximately 10 ms. The method according to claim 1, characterized in that the electric field is repeated for a period of less than 30 minutes. 15. The method according to claim 1, characterized in that the electric field is repeated for a period between 30 and 180 minutes. 16. The method according to claim 1, characterized in that the electric field is applied practically throughout the duration of the glucose absorption case. 17. The method according to claim 1, characterized in that the electric field is applied before a case of expected glucose ingestion. 18. The method according to claim 1, characterized by comprising activating the electric field through a case of glucose ingestion. 19. The method according to claim 1, characterized in that the electric field is applied regardless of a case of ingestion. The method according to claim 1, characterized in that the electric field is applied at least part of the time regardless of a blood glucose level. The method according to claim 1, characterized in that the electric field is applied continuously for at least 24 hours. The method according to claim 1, characterized in that the electric field is applied for a period of at least 15 minutes without sensitization of its effect. 23. The method according to claim 1, characterized in that the electric field is of a magnitude and temporal degree such that it does not significantly change the levels of insulin and glucose in blood in the absence of a case of ingestion. 24. The method according to claim 1, characterized in that the electric field reduces the blood glucose levels by at least 20% of a glucose level rise higher than the fasting initial glucose level. 25. The method according to claim 1, characterized in that the electric field does not increase the blood insulin levels, as measured by an average for five minutes, or by more than 20%. 26. The method according to claim 1, characterized in that the electric field reduces the blood insulin levels, as measured by an accumulated amount for a case of glucose ingestion and compared to a regular response of the person, in more than twenty%. 27. The method according to claim 1, characterized in that it comprises, delaying a gastric emptying by applying a treatment to the stomach. The method according to claim 1, characterized in that the electric field is functional to retard a maximum of glucose for at least one duration of its application. 29. The method according to claim 1, characterized in that the electric field is functional to retard a maximum of glucose for at least 10 minutes. 30. The method according to claim 1, characterized in that the electric field is functional to take a maximum of insulin in less than 10 minutes. 31. The method according to claim 1, characterized in that the electric field is functional to truncate a maximum of insulin. 32. The method according to claim 1, characterized in that the electric field is functional to truncate a maximum of glucose. 33. The method according to claim 1, characterized in that the electrode is not attached to a pancreas.2Ó2 34. The method according to claim 1, characterized in that the electrode is attached to a pancreas. 35. A method for controlling the glucose level, characterized in that it comprises: providing at least one electrode adapted to apply an electric field to a pancreas; and applying an electric field to the functional pancreas to reduce blood glucose levels if they rise and not significantly reduce these levels significantly if they do not rise substantially. 36. The method according to claim 35, characterized in that the electric field reduces the high glucose levels by at least 20%. 37. The method according to claim 35, characterized in that the electric field does not significantly reduce the non-elevated glucose levels by more than 10%. 38. The method according to claim 35, characterized in that the electric field does not damage the exocrine functions of the pancreas. 39. An apparatus for blood glucose control, characterized in that it comprises: at least one electrode adapted to apply an electric field to a pancreas; and circuitry adapted to electrify at least one electrode and configured to electrify the electrode with a non-exciter field so as to compensate for a significant loss of response to the pancreas. 40. The apparatus according to claim 39, characterized in that the circuitry is compensated by causing the secretion of a bolus of insulin. 41. The apparatus according to claim 39, characterized in that the circuitry is compensated by reducing the glucose levels in a non-insulin form. 42. The apparatus according to claim 41, characterized in that the circuitry is compensated for by reducing the secretion of glucagon. 43. The apparatus according to claim 39, characterized in that the circuitry reduces or prevents a substantial increase in insulin secretion during compensation. 44. The apparatus according to claim 39, characterized in that during at least 20% of the cases of ingestion, the circuitry applies only a significant control of insulin levels. 45. The apparatus according to claim 44, characterized in that the apparatus is programmed with an awareness of an insulin therapy based on slow-acting chemicals provided to the pancreas. 46. The apparatus according to claim 39, characterized in that it comprises an automatic ingestion detector to automatically detect a case of ingestion. 47. The apparatus according to claim 39, characterized in that it comprises an automatic glucose detector to automatically detect a situation that requires an important response. 48. The apparatus according to claim 39, characterized in that it comprises an automatic glucose detector for automatically detecting a situation that requires a significant insulin response. 49. The apparatus according to claim 39, characterized in that the response is an important response to insulin. 50. The apparatus according to claim 39, characterized in that the electrode is adapted to be attached to a pancreas. 51. The apparatus according to claim 39, characterized in that the electrode is adapted to be attached to a muscular organ. 52. An apparatus for the control of blood glucose, characterized in that it comprises: at least one electrode adapted to apply an electric field to a pancreas; and circuitry adapted to electrify at least one electrode and configured to electrify the electrode so that it does not significantly reduce elevated blood glucose levels, the circuitry configured to apply the field also when glucose levels are not raised. 53. The apparatus according to claim 52, characterized in that the circuitry is a closed-loop system including the sensitization of the effect of electrification and wherein the circuitry is configured to be over-stimulated in cases of doubt. 54. The apparatus according to claim 52, characterized in that the circuitry is a semi-open cycle system where a series of relatively long stimulation is applied without feedback. 55. The apparatus according to claim 52, characterized in that the circuitry is an open cycle system where a series of stimulation is applied that responds to an activation and without feedback. 56. An apparatus for the control of blood glucose, characterized by comprising: at least one electrode adapted to apply an electric field to the pancreatic tissue; and circuitry adapted to electrify at least one electrode and configured to electrify the electrode so that it lowers glucose levels and does not substantially raise insulin levels above an initial value when glucose levels are raised. 57. The apparatus according to claim 56, characterized by the circuitry is a closed cycle system that includes the sensitization of the effect of electrification and where the circuitry is configured to be over-stimulated in cases of doubt. 58. The apparatus according to claim 56, characterized in that the circuitry is a semi-open cycle system where a series of relatively long stimulation is applied without feedback. 59. The apparatus according to claim 56, characterized in that the circuitry is an open cycle system in which a series of stimulation is applied that responds to an activation and without feedback. 60. The apparatus according to claim 56, characterized in that the circuitry applies a constant voltage field. 61. The apparatus according to claim 56, characterized in that the circuitry applies a constant current field. 62. The apparatus according to claim 56, characterized in that the pancreatic tissue comprises a pancreas xn vxvo. 63. The apparatus according to claim 56, characterized in that the pancreatic tissue comprises a pancreatic tissue implant. 64. The apparatus according to claim 56, characterized in that the initial value is a response to insulin of initial value - of a person for whom the apparatus is used. 65. A method for the control of insulin level, characterized in that it comprises: providing at least one electrode adapted to apply an electric field to a pancreas; and the application of an electric field to the pancreas using at least one electrode in such a way that blood glucose levels are not significantly increased and blood insulin levels are significantly reduced. 66. A method for applying an electric field to a pancreas or a functional and positionally associated tissue, characterized in that it comprises: attaching at least one electro to the tissue other than the pancreas; and electrifying the electrode such that a significant field is applied to the pancreas or associated tissue to control at least one of a level of one < '•. -secretion of the pancreas and a blood glucose level. 67. The method according to claim 66, characterized in that it comprises the use of at least one electrode to also control the feeding habits. 68. An apparatus for the application of an electrical field to a pancreas or a functional and positionally associated tissue, characterized in that it comprises: at least one electrode adapted to be attached to a tissue other than the pancreas; and means for electrifying the electrode such that a significant field is applied to the pancreas or associated tissue to control at least one level of a pancreatic secretion and a blood glucose level.