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. Jørgensen1,2,3⇑,
- Carsten Dirksen1,3,
- Kirstine N. Bojsen-Møller1,3,
- Siv H. Jacobsen1,3,
- Dorte Worm1,
- Dorte L. Hansen1,
- Viggo B. Kristiansen4,
- Lars Naver4,
- Sten Madsbad1 and
- Jens J. Holst2,3
- 1Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
- 2Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
- 3Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
- 4Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark
- Corresponding author: Nils B. Jørgensen, .
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.
- Received January 7, 2013.
- Accepted April 30, 2013.
- © 2013 by the American Diabetes Association.
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