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

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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 Juul Holst

β-cell function is improved 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 an exaggerated glucagon-like peptide 1 (GLP-1) secretion, 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 in regulating glucagon release after RYGB, using the GLP-1 receptor (GLP-1R)-specific antagonist, Exendin(9-39) (Ex-9). Nine patients with type 2 diabetes, were examined before, 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with infusion of saline or Ex-9 in random order. 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 and 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, and the controlof glucagon release and glucose tolerance in patients with type 2 diabetes. ClinicalTrials.gov (NCT01579981).
Original languageEnglish
JournalDiabetes
Volume62
Issue number9
Pages (from-to)3044-3052
Number of pages9
ISSN0012-1797
DOIs
Publication statusPublished - 6 May 2013

ID: 45840173