Research advances in neuromodulation techniques for blood glucose regulation and diabetes intervention_Journal of Biomedical Engineering

Authors：

LIU Hongyun ^1,2 ,  WANG Weidong ^1,2

1. Research Center for Biomedical Engineering, Medical Innovation & Research Division, Chinese PLA General Hospital, Beijing 100853, P. R. China;
2. Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Beijing 100853, P. R. China;

Corresponding author：

Keywords：

Diabetes intervention; Neuromodulation; Vagus nerve stimulation; Ultrasound neuromodulation; Optogenetics

DOI：

10.7507/1001-5515.202307019

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Diabetes and its complications that seriously threaten the health and life of human, has become a public health problem of global concern. Glycemic control remains a major focus in the treatment and management of patients with diabetes. The traditional lifestyle interventions, drug therapies, and surgeries have benefited many patients with diabetes. However, due to problems such as poor patient compliance, drug side effects, and limited surgical indications, there are still patients who fail to effectively control their blood glucose levels. With the development of bioelectronic medicine, neuromodulation techniques have shown great potential in the field of glycemic control and diabetes intervention with its unique advantages. This paper mainly reviewed the research advances and latest achievements of neuromodulation technologies such as peripheral nerve electrical stimulation, ultrasound neuromodulation, and optogenetics in blood glucose regulation and diabetes intervention, analyzed the existing problems and presented prospects for the future development trend to promote clinical research and application of neuromodulation technologies in the treatment of diabetes.

Citation： LIU Hongyun, WANG Weidong. Research advances in neuromodulation techniques for blood glucose regulation and diabetes intervention. Journal of Biomedical Engineering, 2023, 40(6): 1227-1234. doi: 10.7507/1001-5515.202307019 Copy

1.	Larkin H. More adolescents and young adults developing type 2 diabetes around the world. JAMA, 2023, 329(3): 200.
2.	Magliano D J, Boyko E J; IDF Diabetes Atlas 10th edition scientific committee. IDF Diabetes Atlas. 10th ed. Brussels: International Diabetes Federation, 2021.
3.	Sherr J. Seeking simpler solutions with diabetes technology. N Engl J Med, 2022, 387(13): 1228-1229.
4.	Wang L, Peng W, Zhao Z, et al. Prevalence and treatment of diabetes in China, 2013-2018. JAMA, 2021, 326(24): 2498-2506.
5.	Güemes Gonzalez A, Etienne-Cummings R, Georgiou P. Closed-loop bioelectronic medicine for diabetes management. Bioelectron Med, 2020, 6: 11.
6.	Hyun U, Sohn J W. Autonomic control of energy balance and glucose homeostasis. Exp Mol Med, 2022, 54(4): 370-376.
7.	Horn C C, Forssell M, Sciullo M, et al. Hydrogel-based electrodes for selective cervical vagus nerve stimulation. J Neural Eng, 2021, 18: 055008.
8.	Strauss I, Zinno C, Giannotti A, et al. Adaptation and optimization of an intraneural electrode to interface with the cervical vagus nerve// 2021 10th International IEEE/EMBS Conference on Neural Engineering (NER). Italy: IEEE, 2021: 116-119.
9.	Yin J, Ji F, Gharibani P, et al. Vagal nerve stimulation for glycemic control in a rodent model of type 2 diabetes. Obes Surg, 2019, 29(9): 2869-2877.
10.	Payne S C, Ward G, MacIsaac R J, et al. Differential effects of vagus nerve stimulation strategies on glycemia and pancreatic secretions. Physiol Rep, 2020, 8(11): e14479.
11.	Payne S C, Ward G, Fallon J B, et al. Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model. Physiol Rep, 2022, 10(8): e15257.
12.	Guyot M, Simon T, Ceppo F, et al. Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes. Nat Biotechnol, 2019, 37(12): 1446-1451.
13.	Waataja J J, Nihalani R K, Honda C N, et al. Use of a bio-electronic device comprising of targeted dual neuromodulation of the hepatic and celiac vagal branches demonstrated enhanced glycemic control in a type 2 diabetic rat model as well as in an Alloxan treated swine model. Front Neurosci, 2022, 16: 1005932.
14.	Yu Y, He X, Wang Y, et al. Transcutaneous auricular vagal nerve stimulation inhibits limbic-regional P2X7R expression and reverses depressive-like behaviors in Zucker diabetic fatty rats. Neurosci Lett, 2022, 775: 136562.
15.	Zhang Z X, Li S Y, Wang Y, et al. Effect of transcutaneous auricular vagus nerve stimulation on fasting blood glucose and serum insulin concentration in Zucker diabetes fatty rats. World J Acupunct-Mox, 2021, 31(5): 212-217.
16.	Vosseler A, Zhao D, Fritsche L, et al. No modulation of postprandial metabolism by transcutaneous auricular vagus nerve stimulation: a cross-over study in 15 healthy men. Sci Rep, 2020, 10(1): 20466.
17.	Kozorosky E M, Lee C H, Lee J G, et al. Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin. Physiol Rep, 2022, 10(8): e15253.
18.	Meyers E E, Kronemberger A, Lira V, et al. Contrasting effects of afferent and efferent vagal nerve stimulation on insulin secretion and blood glucose regulation. Physiol Rep, 2016, 4(4): e12718.
19.	Stauss H M, Daman L M, Rohlf M M, et al. Effect of vagus nerve stimulation on blood glucose concentration in epilepsy patients - Importance of stimulation parameters. Physiol Rep, 2019, 7(14): e14169.
20.	Liu H, Zhan P, Meng F, et al. Chronic vagus nerve stimulation for drug-resistant epilepsy may influence fasting blood glucose concentration. Biomed Eng Online, 2020, 19(1): 40.
21.	Aristovich K, Donega M, Fjordbakk C, et al. Model-based geometrical optimisation and in vivo validation of a spatially selective multielectrode cuff array for vagus nerve neuromodulation. J Neurosci Methods, 2021, 352: 109079.
22.	Ahmed U, Chang Y C, Zafeiropoulos S, et al. Strategies for precision vagus neuromodulation. Bioelectron Med, 2022, 8(1): 9.
23.	李茜, 陈雪莹, 王冬. 低强度聚焦超声神经调控作用研究进展. 中国医学影像技术, 2021, 37(7): 1078-1081.
24.	Cotero V, Miwa H, Graf J, et al. Peripheral focused ultrasound neuromodulation (pFUS). J Neurosci Methods, 2020, 341: 108721.
25.	Cotero V, Graf J, Miwa H, et al. Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine. Nat Biomed Eng, 2022, 6(6): 683-705.
26.	Chang C H, Fan K C, Cheng Y P, et al. Ultrasound stimulation potentiates management of diabetic hyperglycemia. Ultrasound Med Biol, 2023, 49(5): 1259-1267.
27.	Saab G, Singh T, Chen A W, et al. Modeling of ultrasound stimulation of adolescent pancreas for insulin release therapy. J Ultrasound Med, 2023, 42(8): 1699-1707.
28.	Ashe J, Graf J, Madhavan R, et al. Investigation of liver-targeted peripheral focused ultrasound stimulation (pFUS) and its effect on glucose homeostasis and insulin resistance in type 2 diabetes mellitus: a proof of concept, phase 1 trial. QJM, 2023, 27: hcad098.
29.	于袁欢, 周阳, 王欣怡, 等. 光遗传学照进生物医学研究进展. 合成生物学, 2023, 4(1): 102-140.
30.	Zhang F, Tzanakakis E S. Amelioration of diabetes in a murine model upon transplantation of pancreatic β-cells with optogenetic control of cyclic adenosine monophosphate. ACS Synth Biol, 2019, 8(10): 2248-2255.
31.	Fontaine A K, Ramirez D G, Littich S F, et al. Optogenetic stimulation of cholinergic fibers for the modulation of insulin and glycemia. Sci Rep, 2021, 11(1): 3670.
32.	Li T, Chen X, Qian Y, et al. A synthetic BRET-based optogenetic device for pulsatile transgene expression enabling glucose homeostasis in mice. Nat Commun, 2021, 12(1): 615.
33.	Yu G, Yu Y, Ye H. Constructing a smartphone-controlled semiautomatic theranostic system for glucose homeostasis in diabetic mice. Methods Mol Biol, 2021, 2312: 141-158.
34.	Mansouri M, Xue S, Hussherr M D, et al. Smartphone-flashlight-mediated remote control of rapid insulin secretion restores glucose homeostasis in experimental type-1 diabetes. Small, 2021, 17(35): e2101939.
35.	Lu Q, Wang Z H, Bai S M, et al. Hydrophobicity regulation of energy acceptors confined in mesoporous silica enabled reversible activation of optogenetics for closed-loop glycemic control. J Am Chem Soc, 2023, 145(10): 5941-5951.
36.	He Y, Xu P, Wang C, et al. Estrogen receptor-α expressing neurons in the ventrolateral VMH regulate glucose balance. Nat Commun, 2020, 11(1): 2165.
37.	Kwon E, Joung H Y, Liu S M, et al. Optogenetic stimulation of the liver-projecting melanocortinergic pathway promotes hepatic glucose production. Nat Commun, 2020, 11(1): 6295.
38.	Meng J J, Shen J W, Li G, et al. Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis. Cell, 2023, 186(2): 398-412.e17.
39.	Myers M G Jr, Affinati A H, Richardson N, et al. Central nervous system regulation of organismal energy and glucose homeostasis. Nat Metab, 2021, 3(6): 737-750.
40.	Carter C S, Huang S C, Searby C C, et al. Exposure to static magnetic and electric fields treats type 2 diabetes. Cell Metab, 2020, 32(4): 561-574.

1. Larkin H. More adolescents and young adults developing type 2 diabetes around the world. JAMA, 2023, 329(3): 200.
2. Magliano D J, Boyko E J; IDF Diabetes Atlas 10th edition scientific committee. IDF Diabetes Atlas. 10th ed. Brussels: International Diabetes Federation, 2021.
3. Sherr J. Seeking simpler solutions with diabetes technology. N Engl J Med, 2022, 387(13): 1228-1229.
4. Wang L, Peng W, Zhao Z, et al. Prevalence and treatment of diabetes in China, 2013-2018. JAMA, 2021, 326(24): 2498-2506.
5. Güemes Gonzalez A, Etienne-Cummings R, Georgiou P. Closed-loop bioelectronic medicine for diabetes management. Bioelectron Med, 2020, 6: 11.
6. Hyun U, Sohn J W. Autonomic control of energy balance and glucose homeostasis. Exp Mol Med, 2022, 54(4): 370-376.
7. Horn C C, Forssell M, Sciullo M, et al. Hydrogel-based electrodes for selective cervical vagus nerve stimulation. J Neural Eng, 2021, 18: 055008.
8. Strauss I, Zinno C, Giannotti A, et al. Adaptation and optimization of an intraneural electrode to interface with the cervical vagus nerve// 2021 10th International IEEE/EMBS Conference on Neural Engineering (NER). Italy: IEEE, 2021: 116-119.
9. Yin J, Ji F, Gharibani P, et al. Vagal nerve stimulation for glycemic control in a rodent model of type 2 diabetes. Obes Surg, 2019, 29(9): 2869-2877.
10. Payne S C, Ward G, MacIsaac R J, et al. Differential effects of vagus nerve stimulation strategies on glycemia and pancreatic secretions. Physiol Rep, 2020, 8(11): e14479.
11. Payne S C, Ward G, Fallon J B, et al. Blood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model. Physiol Rep, 2022, 10(8): e15257.
12. Guyot M, Simon T, Ceppo F, et al. Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes. Nat Biotechnol, 2019, 37(12): 1446-1451.
13. Waataja J J, Nihalani R K, Honda C N, et al. Use of a bio-electronic device comprising of targeted dual neuromodulation of the hepatic and celiac vagal branches demonstrated enhanced glycemic control in a type 2 diabetic rat model as well as in an Alloxan treated swine model. Front Neurosci, 2022, 16: 1005932.
14. Yu Y, He X, Wang Y, et al. Transcutaneous auricular vagal nerve stimulation inhibits limbic-regional P2X7R expression and reverses depressive-like behaviors in Zucker diabetic fatty rats. Neurosci Lett, 2022, 775: 136562.
15. Zhang Z X, Li S Y, Wang Y, et al. Effect of transcutaneous auricular vagus nerve stimulation on fasting blood glucose and serum insulin concentration in Zucker diabetes fatty rats. World J Acupunct-Mox, 2021, 31(5): 212-217.
16. Vosseler A, Zhao D, Fritsche L, et al. No modulation of postprandial metabolism by transcutaneous auricular vagus nerve stimulation: a cross-over study in 15 healthy men. Sci Rep, 2020, 10(1): 20466.
17. Kozorosky E M, Lee C H, Lee J G, et al. Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin. Physiol Rep, 2022, 10(8): e15253.
18. Meyers E E, Kronemberger A, Lira V, et al. Contrasting effects of afferent and efferent vagal nerve stimulation on insulin secretion and blood glucose regulation. Physiol Rep, 2016, 4(4): e12718.
19. Stauss H M, Daman L M, Rohlf M M, et al. Effect of vagus nerve stimulation on blood glucose concentration in epilepsy patients - Importance of stimulation parameters. Physiol Rep, 2019, 7(14): e14169.
20. Liu H, Zhan P, Meng F, et al. Chronic vagus nerve stimulation for drug-resistant epilepsy may influence fasting blood glucose concentration. Biomed Eng Online, 2020, 19(1): 40.
21. Aristovich K, Donega M, Fjordbakk C, et al. Model-based geometrical optimisation and in vivo validation of a spatially selective multielectrode cuff array for vagus nerve neuromodulation. J Neurosci Methods, 2021, 352: 109079.
22. Ahmed U, Chang Y C, Zafeiropoulos S, et al. Strategies for precision vagus neuromodulation. Bioelectron Med, 2022, 8(1): 9.
23. 李茜, 陈雪莹, 王冬. 低强度聚焦超声神经调控作用研究进展. 中国医学影像技术, 2021, 37(7): 1078-1081.
24. Cotero V, Miwa H, Graf J, et al. Peripheral focused ultrasound neuromodulation (pFUS). J Neurosci Methods, 2020, 341: 108721.
25. Cotero V, Graf J, Miwa H, et al. Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine. Nat Biomed Eng, 2022, 6(6): 683-705.
26. Chang C H, Fan K C, Cheng Y P, et al. Ultrasound stimulation potentiates management of diabetic hyperglycemia. Ultrasound Med Biol, 2023, 49(5): 1259-1267.
27. Saab G, Singh T, Chen A W, et al. Modeling of ultrasound stimulation of adolescent pancreas for insulin release therapy. J Ultrasound Med, 2023, 42(8): 1699-1707.
28. Ashe J, Graf J, Madhavan R, et al. Investigation of liver-targeted peripheral focused ultrasound stimulation (pFUS) and its effect on glucose homeostasis and insulin resistance in type 2 diabetes mellitus: a proof of concept, phase 1 trial. QJM, 2023, 27: hcad098.
29. 于袁欢, 周阳, 王欣怡, 等. 光遗传学照进生物医学研究进展. 合成生物学, 2023, 4(1): 102-140.
30. Zhang F, Tzanakakis E S. Amelioration of diabetes in a murine model upon transplantation of pancreatic β-cells with optogenetic control of cyclic adenosine monophosphate. ACS Synth Biol, 2019, 8(10): 2248-2255.
31. Fontaine A K, Ramirez D G, Littich S F, et al. Optogenetic stimulation of cholinergic fibers for the modulation of insulin and glycemia. Sci Rep, 2021, 11(1): 3670.
32. Li T, Chen X, Qian Y, et al. A synthetic BRET-based optogenetic device for pulsatile transgene expression enabling glucose homeostasis in mice. Nat Commun, 2021, 12(1): 615.
33. Yu G, Yu Y, Ye H. Constructing a smartphone-controlled semiautomatic theranostic system for glucose homeostasis in diabetic mice. Methods Mol Biol, 2021, 2312: 141-158.
34. Mansouri M, Xue S, Hussherr M D, et al. Smartphone-flashlight-mediated remote control of rapid insulin secretion restores glucose homeostasis in experimental type-1 diabetes. Small, 2021, 17(35): e2101939.
35. Lu Q, Wang Z H, Bai S M, et al. Hydrophobicity regulation of energy acceptors confined in mesoporous silica enabled reversible activation of optogenetics for closed-loop glycemic control. J Am Chem Soc, 2023, 145(10): 5941-5951.
36. He Y, Xu P, Wang C, et al. Estrogen receptor-α expressing neurons in the ventrolateral VMH regulate glucose balance. Nat Commun, 2020, 11(1): 2165.
37. Kwon E, Joung H Y, Liu S M, et al. Optogenetic stimulation of the liver-projecting melanocortinergic pathway promotes hepatic glucose production. Nat Commun, 2020, 11(1): 6295.
38. Meng J J, Shen J W, Li G, et al. Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis. Cell, 2023, 186(2): 398-412.e17.
39. Myers M G Jr, Affinati A H, Richardson N, et al. Central nervous system regulation of organismal energy and glucose homeostasis. Nat Metab, 2021, 3(6): 737-750.
40. Carter C S, Huang S C, Searby C C, et al. Exposure to static magnetic and electric fields treats type 2 diabetes. Cell Metab, 2020, 32(4): 561-574.

Journal of Biomedical Engineering

Research advances in neuromodulation techniques for blood glucose regulation and diabetes intervention

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content