276-LB: STR-Mediated Glucose Sensing and GLUT2-Regulated Glucose Absorption Are Repaired by DJB Surgery in Diabetic Rats

Abstract

Abstract: Our previous study demonstrated that duodenal-jejunal bypass (DJB) ameliorated glycemic control in a diabetic rat model but the underlying mechanisms are still unclear. This study aimed to identify the regulatory function of sweet taste receptors and glucose transporters within the DJB-remodeled small intestine and gut peptide secretion. DJB or sham surgeries were performed in streptozotocin (STZ)-induced diabetic rats. The blood GLP-1 and GLP-2 levels were evaluated under feeding and fasting conditions. The effects of sweet taste receptors (STR) inhibition on glucose control were measured in vivo with lactisole (STR inhibitor). The results showed that the glucose tolerance was improved in DJB-operated rats compared with Sham group, similar to that of normal control rats without significant differences in food intake and body weight. The plasma levels of insulin were increased after DJB in both feeding and fasting conditions. The plasma GLP-1 levels of DJB rats were increased under diet-fed condition, and GLP-2 levels of DJB rats were increased after fasting. The villus height and crypt depth were significantly increased in the intestinal alimentary limb (A limb) of DJB-operated rats, while decreased in the biliopancreatic limb (BP limb). The expression levels of T1R2, T1R3, sweet taste signaling effector Gα-gustducin and glucose transporters SGLT1, GLUT2 was downregulated in the BP and common limbs, but was elevated in the A limb after DJB. However, the beneficial effects of DJB on glood control was abolished in the presence of lactisole. Furthermore, the immunofluorescence results displayed that GLUT2 localization was normalized after DJB. In conclusion, these findings indicate that DJB ameliorates glycemic control probably via repairing sweet taste receptor-mediated glucose sensing and absorption with the responses of GLP-1 and GLP-2 to dietary carbohydrate. Keywords: Sweet taste receptor; Lactisole; GLUT2; SGLT1; GLP-1; GLP-2; DJB; Disclosure A. Wang: None. R. Kou: None. X. Zhao: None. S. Sun: None. Y. Wang: None. Z. Gao: None. Funding National Natural Science Foundation of China (82070856, 82100842); Natural Science Foundation of Shandong Province (ZR201807090175, ZR2020QH084)