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

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.