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

  1. Jens J Holst1,3
  1. 1Dept. of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
  2. 2Dept. of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  3. 3Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
  4. 4Dept. of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark
  1. Corresponding author: Nils B Jørgensen, nils.bruun.joergensen{at}regionh.dk.

Abstract

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).

  • Received January 7, 2013.
  • Accepted April 29, 2013.

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  1. Diabetes
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