Exaggerated glucagon-like peptide 1 response is important for improved ?-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes.

ABSTRACT: ?-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving ?-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)-specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, ?-cell glucose sensitivity (?-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect ?-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, ?-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in ?-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.

SUBMITTER: Jorgensen NB 

PROVIDER: S-EPMC3749359 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature