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1. WO2016141184 - GLUCOSE REGULATION VIA ELECTRICAL STIMULATION OF NERVES INNERVATING THE LIVER

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[ EN ]

WHAT IS CLAIMED:

1. A method for causing a perturbation of blood glucose level in a subject, comprising: selectively inhibiting neural activity of at least one of a hepatic branch of the subject's vagus nerve or the subject's greater splanchnic nerve using electrical stimulation having a frequency greater than about 5 kHz, wherein the selective inhibition of neural activity causes the subject's blood glucose level to increase or decrease as compared to a baseline level.

2. The method of claim 1, further comprising selectively exciting neural activity of at least one of the hepatic branch of the subject's vagus nerve or the subject's greater splanchnic nerve using electrical stimulation, wherein the selective excitation and inhibition of neural activity causes the subject's blood glucose level to increase or decrease as compared to the baseline level.

3. The method of claim 2, wherein neural activity of the hepatic branch of the subject's vagus nerve is selectively excited using electrical stimulation.

4. The method of any of claims 1-3, wherein neural activity of the subject's greater splanchnic nerve is selectively inhibited using electrical stimulation having a frequency greater than about 5 kHz.

5. The method of any of claims 1-4, wherein neural activity of at least one of the hepatic branch of the subject's vagus nerve or the subject's greater splanchnic nerve is selectively inhibited using electrical stimulation having a frequency from about 5 kHz to about 100 KHz.

6. The method of claim 5, wherein the electrical stimulation delivers a current with an amplitude from about 50 μΑ to about 50 mA.

7. The method of any of claims 2-5, wherein neural activity of at least one of the hepatic branch of the subject's vagus nerve or the subject's greater splanchnic nerve is selectively excited using electrical stimulation having a frequency from about 1 Hz to about 200 Hz.

8. The method of claim 7, wherein the electrical stimulation delivers a current with an amplitude from about 50 μΑ to about 50 mA.

9. The method of any of claims 1-8, further comprising:

administering a substance to the subject;

measuring the subject's blood glucose level at each of a plurality of time intervals;

adjusting one or more stimulation parameters based on the subject's measured blood glucose level; and

altering a glucose load associated with the substance through the selective excitation or inhibition of neural activity.

10. The method of claim 9, wherein the substance is administered to the subject orally or through injection.

11. The method of any of claims 1-10, wherein the selective excitation or inhibition of neural activity further causes a change in level of a metabolite or enzyme.

12. The method of any of claims 1-11, further comprising providing a first electrode at a portion of the hepatic branch of the subject's vagus nerve and a second electrode at a portion of the subject's greater splanchnic nerve.

13. The method of claim 12, wherein the first electrode is provided between the subject's liver and the subject's vagal trunk.

14. The method of any of claims 12 or 13, wherein the second electrode is provided between the subject's suprarenal ganglia and celiac ganglia.

15. The method of any of claims 12-14, wherein at least one of the first electrode or the second electrode is a monopolar, bipolar, or tripolar electrode.

16. The method of any of claims 1-15, further comprising monitoring the subject's blood glucose level.

17. The method of claim 16, further comprising controlling the selective excitation or inhibition of neural activity based on the subject's blood glucose level.

18. The method of any of claims 1-16, further comprising controlling the selective excitation or inhibition of neural activity based on user input.

19. The method of any of claims 1-16, further comprising controlling the selective excitation or inhibition of neural activity based on a predetermined time schedule.

20. A method for causing a perturbation of blood glucose level in a subject, comprising: providing a first electrode at a portion of a hepatic branch of the subject's vagus nerve; providing a second electrode at a portion of the subject's greater splanchnic nerve;

providing a stimulus generator operably coupled with the first electrode and the second electrode; and

using the stimulus generator, providing a first stimulus signal to the first electrode, the first stimulus signal being configured to energize the first electrode and excite neural activity of the hepatic branch of the subject's vagus nerve, and providing a second stimulus signal to the second electrode, the second stimulus signal being configured to energize the second electrode and inhibit neural activity of the subject's greater splanchnic nerve.

21. The method of claim 20, wherein the subject's blood glucose level increases as compared to a baseline level in response to providing the first stimulus or providing the second stimulus signal.

22. The method of any of claims 20 or 21, wherein the subject's blood glucose level decreases as compared to a baseline level in response to providing the first stimulus signal or providing the second stimulus signal.

23. The method of any of claims 20-22, wherein the first stimulus signal is a waveform applied at a frequency from about 1 Hz to about 200 Hz.

24. The method of claim 23, wherein the first stimulus signal delivers a current with an amplitude from about 50 μΑ to about 50 mA.

25. The method of any of claims 20-24, wherein the second stimulus signal is a waveform applied at a frequency from about 1 kHz to about 100 kHz.

26. The method of claim 25, wherein the second stimulus signal delivers a current with an amplitude from about 50 μΑ to about 50 mA.

27. The method of any of claims 20-26, wherein at least one of the first electrode or the second electrode is a monopolar, bipolar, or tripolar electrode.

28. The method of any of claims 20-27, wherein the first electrode is located between the subject's liver and the subject's vagal trunk.

29. The method of any of claims 20-28, wherein the second electrode is located between the subject's suprarenal ganglia and celiac ganglia.

30. The method of any of claims 20-29, wherein the stimulus generator is a voltage source.

31. The method of any of claims 20-29, wherein the stimulus generator is a current source.

32. The method of any of claims 20-31, wherein at least one of the first electrode, the second electrode, or the stimulus generator are implanted in the subject's body.

33. The method of any of claims 20-32, further comprising providing a control unit operably coupled with the stimulus generator, wherein the control unit comprises a processor and memory operably coupled to the processor.

34. The method of claim 33, wherein the control unit is configured to receive a user input and, in response to the user input, transmit a control signal to the stimulus generator to initiate providing the first stimulus signal or the second stimulus signal.

35. The method of claim 34, wherein the control unit is configured to transmit at predetermined time intervals a control signal to the stimulus generator to initiate providing the first stimulus signal or the second stimulus signal.

36. The method of any of claims 33-35, further comprising providing a glucose sensor for monitoring the subject's blood glucose level.

37. The method of claim 36, wherein the glucose sensor is implanted in the subject's body.

38. The method of any of claims 36 or 37, wherein the control unit is configured to transmit at a predetermined blood glucose level a control signal to the stimulus generator to initiate providing the first stimulus signal or the second stimulus signal.

39. The method of claim 38, wherein the predetermined blood glucose level is adjustable by a user.

40. The method of any of claims 32-39, wherein the control unit further comprises at least one of a display device or an interface device.

41. A device for causing a perturbation of blood glucose level in a subject, comprising: a first electrode configured to attach to a portion of a hepatic branch of the subject's vagus nerve;

a second electrode configured to attach to a portion of the subject's greater splanchnic nerve;

a stimulus generator operably coupled with the first electrode and the second electrode, the stimulus generator being configured to provide stimulus signals to at least one of the first electrode and the second electrode; and

a control unit operably coupled with the stimulus generator, the control unit comprising a processor and memory operably coupled to the processor, wherein the control unit is configured to control the stimulus generator to:

provide a first stimulus signal configured to selectively excite neural activity of at least one of the hepatic branch of the subject's vagus nerve or the subject's greater splanchnic nerve; and

provide a second stimulus signal having a frequency greater than about 5 kHz and configured to selectively inhibit neural activity of at least one of the hepatic branch of the subject's vagus nerve or the subject's greater splanchnic nerve, wherein the selective excitation and inhibition of neural activity causes the subject's blood glucose level to increase or decrease as compared to a baseline level.

42. A device for causing a perturbation of blood glucose level in a subject, comprising:

a first electrode configured to attach to a portion of a hepatic branch of the subject's vagus nerve;

a second electrode configured to attach to a portion of the subject's greater splanchnic nerve;

a stimulus generator operably coupled with the first electrode and the second electrode, the stimulus generator being configured to provide stimulus signals to the first electrode and the second electrode; and

a control unit operably coupled with the stimulus generator, the control unit comprising a processor and memory operably coupled to the processor, wherein the control unit is configured to control the stimulus generator to:

provide a first stimulus signal to the first electrode, the first stimulus signal being configured to excite neural activity of the hepatic branch of the subject's vagus nerve; and provide a second stimulus signal to the second electrode, the second stimulus signal being configured to inhibit neural activity of the subject's greater splanchnic nerve.