Neuromodulation to target glucose transporter and/or incretin pathways
The subject matter of the present disclosure generally relates to techniques for neuromodulation that include applying energy (e.g., ultrasound energy) into the tissue to cause a change in a glucose transporter pathway molecule and/or an incretin pathway molecule. In one embodiment, the neuromodulation is performed as a treatment of a metabolic disorder.
1. A method for treating a subject having a metabolic disorder, comprising:
applying ultrasound energy to an internal tissue and stimulating sensory neurons within the internal tissue of the subject having the metabolic disorder to cause a change to a glucose transporter pathway molecule and/or an incretin pathway molecule in the subject to treat the metabolic disorder, wherein the ultrasound energy is applied at a low power by an extracorporeal energy application device;
measuring the change or an indication of the change in the subject, wherein the change of the glucose transporter pathway molecule and/or the incretin pathway molecule is at an internal organ that is distal from the internal tissue; and
determining, based on the measuring, that the ultrasound energy caused the change to the glucose transporter pathway molecule and/or the incretin pathway molecule to treat the subject.
2. The method of claim 1 , wherein the internal tissue is a liver.
3. The method of claim 2 , wherein the applying comprises applying the ultrasound energy to only a subregion of the liver.
4. The method of claim 3 , wherein the subregion is a porta hepatis of the liver.
5. The method of claim 1 , wherein the internal tissue is a gastrointestinal tissue.
6. The method of claim 1 , comprising imaging the internal tissue to identify a region of interest of the internal tissue and applying the ultrasound energy to the region of interest.
7. The method of claim 1 , wherein the metabolic disorder is type 2 diabetes mellitus.
8. The method of claim 1 , wherein the metabolic disorder is hyperglycemia.
9. The method of claim 1 , wherein the metabolic disorder is insulin resistance.
10. The method of claim 1 , wherein the change comprises a concentration change, an activity change, and/or a location change of the glucose transporter pathway molecule and/or the incretin pathway molecule.
11. The method of claim 1 , wherein the glucose transporter pathway molecule and/or the incretin pathway molecule is one or more of sodium glucose co-transporter 2 protein (SGLT2), glucose transporter 2 (GLUT-2), glucose transporter 4 (GLUT-4) or glucagon-like peptide-1 (GLP-1).
12. The method of claim 1 , wherein the ultrasound energy is applied with a temporal average intensity less than 35 W/cm 2 .
13. The method of claim 12 , wherein the temporal average intensity is in a range of 1 mW/cm 2 and 30,000 mW/cm 2 .
14. The method of claim 1 , wherein no significant change of the glucose transporter pathway molecule and/or the incretin pathway molecule occurs at the internal tissue.
15. A system for treating a metabolic disorder in a subject, the system comprising:
an ultrasound application device configured to apply low power ultrasound energy to an internal tissue of the subject to stimulate sensory neurons within the internal tissue;
a controller adapted to control the ultrasound application device to apply the ultrasound energy to cause a change to a glucose transporter pathway molecule and/or an incretin pathway molecule in the subject at an internal organ that is distal from the internal tissue; and
an assessment device configured to receive an input indicative of the change.
16. The system of claim 15 , wherein the assessment device is a glucose monitor.
17. The system of claim 15 , wherein the ultrasound application device comprises an ultrasound transducer.
18. The system of claim 15 , wherein the controller is configured to change one or more parameters that control the ultrasound application based on the input.
19. A method for treating a subject having a metabolic disorder, comprising:
selecting a region of interest in a liver of the subject;
applying ultrasound energy at a low power to the region of interest of the liver and stimulating sensory neurons within the liver to cause a change to a glucose transporter pathway molecule and/or an incretin pathway molecule in an internal organ that is distal from the liver in the subject;
measuring a blood glucose concentration, an excreted glucose concentration, or both, of the subject; and
determining that the ultrasound energy caused the change to the glucose transporter pathway molecule and/or the incretin pathway molecule to treat the subject based on the blood glucose concentration, the excreted glucose concentration, or both.
20. The method of claim 19 , wherein determining that the ultrasound energy caused the change comprises determining that the blood glucose concentration has decreased relative to a baseline or threshold and that the excreted glucose concentration has increased relative to a baseline or threshold.
21. A method for treating a subject having a metabolic disorder, comprising:
selecting a region of interest in a gastrointestinal tissue and stimulating sensory neurons within the gastrointestinal tissue of the subject;
applying ultrasound energy at a low power to the region of interest in the gastrointestinal tissue to cause a change to a glucose transporter pathway molecule and/or an incretin pathway molecule, wherein the change of the glucose transporter pathway molecule and/or the incretin pathway molecule is at an internal organ that is distal from the gastrointestinal tissue;
measuring a blood glucose concentration, a blood glucagon-like peptide 1 concentration, or both, of the subject; and
determining that the ultrasound energy caused the change to the glucose transporter pathway molecule and/or the incretin pathway molecule to treat the subject based on the blood glucose concentration, the blood glucagon-like peptide 1 concentration, or both.
22. The method of claim 21 , wherein the region of interest is in a jejunum region of a small intestine.