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

Nils B Jørgensen, Carsten Dirksen, Kirstine N Bojsen-Møller, Siv H Jacobsen, Dorte Worm, Dorte L Hansen, Viggo B Kristiansen, Lars Naver, Sten Madsbad, Jens J Holst

Index: Diabetes 62(9) , 3044-52, (2013)

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Abstract

β-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 β-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, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-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 β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.