Contribution of endogenous glucagon-like peptide-1 to changes in glucose metabolism and islet function in people with type 2 diabetes four weeks after Roux-en-Y gastric bypass (RYGB).

ABSTRACT: Glucagon-Like Peptide-1 (GLP-1) is an insulin secretagogue which is elevated after Roux-en-Y Gastric Bypass (RYGB). However, its contribution to glucose metabolism after RYGB remains uncertain. AIMS:We tested the hypothesis that GLP-1 lowers postprandial glucose concentrations and improves ?-cell function after RYGB. MATERIALS AND METHODS:To address these questions we used a labeled mixed meal to assess glucose metabolism and islet function in 12 obese subjects with type 2 diabetes studied before and four weeks after RYGB. During the post-RYGB study subjects were randomly assigned to receive an infusion of either saline or Exendin-9,39 a competitive antagonist of GLP-1 at its receptor. Exendin-9,39 was infused at 300?pmol/kg/min for 6?h. All subjects underwent RYGB for medically-complicated obesity. RESULTS:Exendin-9,39 resulted in increased integrated incremental postprandial glucose concentrations (181?±?154 vs. 582?±?129?mmol per 6?h, p?=?0.02). In contrast, this was unchanged in the presence of saline (275?±?88 vs. 315?±?66?mmol per 6?h, p?=?0.56) after RYGB. Exendin-9,39 also impaired ?-cell responsivity to glucose but did not alter Disposition Index (DI). CONCLUSIONS:These data indicate that the elevated GLP-1 concentrations that occur early after RYGB improve postprandial glucose tolerance by enhancing postprandial insulin secretion.

SUBMITTER: Shah M 

PROVIDER: S-EPMC6401231 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature