Skip to main content
Log in

Hypoglycemic Effects of Intestinal Electrical Stimulation by Enhancing Nutrient-Stimulated Secretion of GLP-1 in Rats

  • Original Contributions
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Purpose

To find out the best location for intestinal electrical stimulation (IES) to decrease hyperglycemia, and mechanisms involving intraluminal nutrients and plasma glucagon-like peptide-1 (GLP-1)

Materials and Methods

Eight rats had electrodes implanted at the duodenum and ileums for IES. The oral glucose tolerance test (OGTT) was performed with IES and sham-IES and with/without GLP-1 antagonist, exendin. To study the role of intraluminal nutrients, the experiment was repeated using intraperitoneal glucose tolerance test (IPGTT). Glucagon was administrated in the OGTT/IPGTT to induce temporary hyperglycemia.

Results

(1) In the OGTT, IES at the duodenum reduced blood glucose from 30 to 120 min after oral glucose (P < 0.05, vs. sham-IES) and the hypoglycemic effect was more potent than IES at the ileum. (2) The hypoglycemic effect of IES was absent in IPGTT experiment, suggesting the important role of intraluminal nutrients. (3) An increase in GLP-1 was noted in the OGTT with IES at the duodenum in comparison with sham-IES. Moreover, the blocking effect of exendin suggested the role of GLP-1 in the hypoglycemic effect of IES.

Conclusions

The best stimulation location for IES to decrease hyperglycemia is in the duodenum. The hypoglycemic effect of IES is attributed to the enhancement in nutrient-stimulated release of GLP-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Pfeiffer AF, Klein HH. The treatment of type 2 diabetes. Dtsch Arztebl Int. 2014;111(5):69–81. quiz 82

    Google Scholar 

  2. Puzziferri N, Roshek 3rd TB, Mayo HG, et al. Long-term follow-up after bariatric surgery: a systematic review. JAMA. 2014;312(9):934–42.

    Article  CAS  Google Scholar 

  3. Maggard-Gibbons M, Maglione M, Livhits M, et al. Bariatric surgery for weight loss and glycemic control in nonmorbidly obese adults with diabetes: a systematic review. JAMA. 2013;309(21):2250–61.

    Article  CAS  Google Scholar 

  4. Qaseem A, Barry MJ, Humphrey LL, et al. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(4):279–90.

    Article  Google Scholar 

  5. Nathan DM. Diabetes: advances in diagnosis and treatment. JAMA. 2015;314(10):1052–62.

    Article  CAS  Google Scholar 

  6. Chen JD, Yin J, Wei W. Electrical therapies for gastrointestinal motility disorders. Expert Rev Gastroenterol Hepatol. 2017;11(5):407–18.

    Article  CAS  Google Scholar 

  7. Zhao X, Yin J, Chen J, et al. Inhibitory effects and mechanisms of intestinal electrical stimulation on gastric tone, antral contractions, pyloric tone, and gastric emptying in dogs. Am J Physiol Regul Integr Comp Physiol. 2009;296(1):R36–42.

    Article  CAS  Google Scholar 

  8. Li S, Zhu W, Zhang S, et al. Chronic intestinal electrical stimulation improves glucose intolerance and insulin resistance in diet-induced obesity rats. Obesity (Silver Spring). 2017;25(6):1061–8.

    Article  CAS  Google Scholar 

  9. Wan X, Yin J, Foreman R, et al. An optimized IES method and its inhibitory effects and mechanisms on food intake and body weight in diet-induced obese rats: IES for obesity. Obes Surg. 2017;27(12):3215–22.

    Google Scholar 

  10. Ouyang X, Li S, Foreman R, et al. Hyperglycemia-induced small intestinal dysrhythmias attributed to sympathovagal imbalance in normal and diabetic rats. Neurogastroenterol Motil. 2015;27(3):406–15.

    Article  CAS  Google Scholar 

  11. Khawaled R, Blumen G, Fabricant G, et al. Intestinal electrical stimulation decreases postprandial blood glucose levels in rats. Surg Obes Relat Dis. 2009;5(6):692–7.

    Article  Google Scholar 

  12. Liu J, Xiang Y, Qiao X, et al. Hypoglycemic effects of intraluminal intestinal electrical stimulation in healthy volunteers. Obes Surg. 2011;21(2):224–30.

    Article  Google Scholar 

  13. Li S, Chen JD. Pulse width-dependent effects of intestinal electrical stimulation for obesity: role of gastrointestinal motility and hormones. Obes Surg. 2017;27(1):70–7.

    Article  Google Scholar 

  14. Williams DL, Baskin DG, Schwartz MW. Evidence that intestinal glucagon-like peptide-1 plays a physiological role in satiety. Endocrinology. 2009;150(4):1680–7.

    Article  CAS  Google Scholar 

  15. Gibbons CH, Goebel-Fabbri A. Microvascular complications associated with rapid improvements in glycemic control in diabetes. Curr Diab Rep. 2017;17(7):48.

    Article  Google Scholar 

  16. Kawanami D, Matoba K, Sango K, et al. Incretin-based therapies for diabetic complications: basic mechanisms and clinical evidence. Int J Mol Sci. 2016;17(8).

  17. Pecoits-Filho R, Abensur H, Betônico CC, et al. Interactions between kidney disease and diabetes: dangerous liaisons. Diabetol Metab Syndr. 2016;8:50.

    Article  Google Scholar 

  18. Azami M, Sharifi A, Norozi S, et al. Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance in patients with thalassemia major in Iran: a meta-analysis study. Caspian J Intern Med. 2017;8(1):1–15.

    Google Scholar 

  19. Thrasher J. Pharmacologic management of type 2 diabetes mellitus: available therapies. Am J Med. 2017;130(6S):S4–17.

    Article  CAS  Google Scholar 

  20. Yin J, Zhang J, Chen JD. Inhibitory effects of intestinal electrical stimulation on food intake, weight loss and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol. 2007;293(1):R78–82.

    Article  CAS  Google Scholar 

  21. Aberle J, Busch P, Veigel J, et al. Duodenal electric stimulation: results of a first-in-man study. Obes Surg. 2016;26(2):369–75.

    Article  Google Scholar 

  22. Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology. 1986;90(6):1919–25.

    Article  CAS  Google Scholar 

  23. Horowitz M, Edelbroek M, Fraser R, et al. Disordered gastric motor function in diabetes mellitus. Recent insights into prevalence, pathophysiology, clinical relevance, and treatment. Scand J Gastroenterol. 1991;26(7):673–84.

    Article  CAS  Google Scholar 

  24. Steinberg BE, Glass L, Shrier A, et al. The role of heterogeneities and intercellular coupling in wave propagation in cardiac tissue. Philos Trans A Math Phys Eng Sci. 2006;364(1842):1299–311.

    Article  Google Scholar 

  25. Camilleri M, Malagelada JR. Abnormal intestinal motility in diabetics with the gastroparesis syndrome. Eur J Clin Investig. 1984;14(6):420–7.

    Article  CAS  Google Scholar 

  26. Nowak TV, Harrington B, Kalbfleisch JH, et al. Evidence for abnormal cholinergic neuromuscular transmission in diabetic rat small intestine. Gastroenterology. 1986;91(1):124–32.

    Article  CAS  Google Scholar 

  27. Wang WF, Yin JY, De Dz Chen J. Acceleration of small bowel transit in a canine hypermotility model with intestinal electrical stimulation. J Dig Dis. 2015;16(3):135–42.

    Article  CAS  Google Scholar 

  28. Sun Y, Chen JD. Intestinal electric stimulation accelerates whole gut transit and promotes fat excrement in conscious rats. Int J Obes. 2009;33(8):817–23.

    Article  CAS  Google Scholar 

  29. Foster C, Costill DL, Fink WJ. Gastric emptying characteristics of glucose and glucose polymer solutions. Res Q Exerc Sport. 1980;51(2):299–305.

    Article  CAS  Google Scholar 

  30. Sandoval D, Dunki-Jacobs A, Sorrell J, et al. Impact of intestinal electrical stimulation on nutrient-induced GLP-1 secretion in vivo. Neurogastroenterol Motil. 2013;25(8):700–5.

    Article  CAS  Google Scholar 

  31. Gribble FM, Reimann F. Signalling in the gut endocrine axis. Physiol Behav. 2017;176:183–8.

    Article  CAS  Google Scholar 

  32. Vahl T, D'Alessio D. Enteroinsular signaling: perspectives on the role of the gastrointestinal hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide in normal and abnormal glucose metabolism. Curr Opin Clin Nutr Metab Care. 2003;6(4):461–8.

    CAS  Google Scholar 

  33. MacDonald PE, El-Kholy W, Riedel MJ, et al. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes. 2002;51(Suppl 3):S434–42.

    Article  CAS  Google Scholar 

  34. Orskov C. Glucagon-like peptide-1, a new hormone of the entero-insular axis. Diabetologia. 1992;35(8):701–11.

    CAS  Google Scholar 

  35. Straub SG, Sharp GW. Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab Res Rev. 2002;18(6):451–63.

    Article  CAS  Google Scholar 

  36. Kim DS, Choi HI, Wang Y, et al. A new treatment strategy for Parkinson’s disease through the gut-brain axis: the glucagon-like peptide-1 receptor pathway. Cell Transplant. 2017;26(9):1560–71.

    Article  Google Scholar 

  37. Mojsov S, Weir GC, Habener J. Insulinotropin: glucagon-like peptide 1 (7–37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest. 1987;79(2):616–9.

    Article  CAS  Google Scholar 

  38. Yin J, Kuang J, Chandalia MT, et al. Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance. Am J Physiol Regul Integr Comp Physiol. 2014;307(3):R332–9.

    Article  CAS  Google Scholar 

  39. Knauf C, Cani PD, Perrin C, et al. Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage. J Clin Invest. 2005;115(12):3554–63.

    Article  CAS  Google Scholar 

  40. Guglielmi V, Sbraccia P. GLP-1 receptor independent pathways: emerging beneficial effects of GLP-1 breakdown products. Eat Weight Disord. 2017;22(2):231–40.

    Article  Google Scholar 

  41. Wootten D, Reynolds CA, Smith KJ, et al. Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor. Biochem Pharmacol. 2016;118:68–87.

    Article  CAS  Google Scholar 

  42. Nance KD, Days EL, Weaver CD, et al. Discovery of a novel series of orally bioavailable and CNS penetrant glucagon-like peptide-1 receptor (GLP-1R) noncompetitive antagonists based on a 1,3-disubstituted-7-aryl-5,5-bis(trifluoromethyl)-5,8-dihydropyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione core. J Med Chem. 2017;60(4):1611–6.

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported in part by a VA MERIT grant (1I01BX002010).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jiande D. Z. Chen.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

A Statement of Animal Rights/Ethical Approval

All procedures in this study were approved by the Animal Care and Use Committee of the Veterans Affairs Medical Center (Oklahoma City, OK).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ye, F., Liu, Y., Li, S. et al. Hypoglycemic Effects of Intestinal Electrical Stimulation by Enhancing Nutrient-Stimulated Secretion of GLP-1 in Rats. OBES SURG 28, 2829–2835 (2018). https://doi.org/10.1007/s11695-018-3257-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11695-018-3257-1

Keywords

Navigation