GLP-1 enhances beta-cell response to protein ingestion and bariatric surgery amplifies it.

Protein ingestion stimulates β-cell secretion and alters glucose flux. Enhanced action of glucagon-like peptide 1 (GLP-1) and increased plasma glucose excursion contribute to prandial hyperinsulinemia after gastric bypass surgery (GB) and sleeve gastrectomy (SG). We examined the contribution of endogenous GLP-1 to glucose kinetics and β-cell response to protein ingestion under basal glucose concentrations in humans, and whether these responses are affected by rerouted gut after GB or SG. Glucose fluxes, insulin secretion rate (ISR), and incretin responses to a 50-gram oral protein load were compared between 10 non-diabetic individuals with GB, 9 matched subjects with SG and 7 non-operated controls (CN) with and without intravenous infusion of exendin-(9-39) [Ex-9), a specific GLP-1 receptor (GLP-1R) antagonist. Blocking GLP-1R increased the plasma glucose concentration before and after protein ingestion in all 3 groups (p<0.05) and decreased β-cell sensitivity to glucose in the first 30 minutes of protein ingestion (p<0.05). Reduction in the prandial ISR These findings are consistent with both a pancreatic and extrapancreatic role for GLP-1 during protein ingestion in humans, and GLP-1 actions are exaggerated by bariatric surgery.