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Am J Physiol Endocrinol Metab. 2016 Apr 1;310(7):E505-14. doi: 10.1152/ajpendo.00471.2015. Epub 2016 Jan 19.

Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery.

Author information

1
Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Maria.Saur.Svane@regionh.dk.
2
Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
3
Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark;
4
Department of Surgical and Medical Gastroenterology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; and.
5
NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and β-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin-(9-39) (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose-tolerant patients were studied after RYGB in a randomized, placebo-controlled, 4-day crossover study with standard mixed-meal tests and concurrent administration of placebo, oral sitagliptin, Ex-9 infusion, or combined Ex-9-sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated β-cell function, and aggravated postprandial hyperglucagonemia compared with placebo, whereas sitagliptin had no effect despite two- to threefold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or β-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4-sensitive glucose-lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB.

KEYWORDS:

Roux-en-Y gastric bypass; dipeptidyl peptidase-4 inhibition; exendin-(9–39); glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide

PMID:
26786780
DOI:
10.1152/ajpendo.00471.2015
[Indexed for MEDLINE]
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