Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency

Mohamad Mokadem; Juliet F Zechner; Robert F Margolskee; Daniel J Drucker; Vincent Aguirre

doi:10.1016/j.molmet.2013.11.010

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Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency

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Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency

Mohamad Mokadem, Juliet F Zechner, Robert F Margolskee, Daniel J Drucker and Vincent Aguirre

Molecular metabolism (Germany), Vol.3(2), pp.191-201

04/2014

DOI: 10.1016/j.molmet.2013.11.010

PMID: 24634822

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Abstract

Glucagon-like peptide-1 (GLP-1) secretion is greatly enhanced after Roux-en-Y gastric bypass (RYGB). While intact GLP-1exerts its metabolic effects via the classical GLP-1 receptor (GLP-1R), proteolytic processing of circulating GLP-1 yields metabolites such as GLP-1(9–36)amide/GLP-1(28–36)amide, that exert similar effects independent of the classical GLP-1R. We investigated the hypothesis that GLP-1, acting via these metabolites or through its known receptor, is required for the beneficial effects of RYGB using two models of functional GLP-1 deficiency – α-gustducin-deficient (α-Gust−/−) mice, which exhibit attenuated nutrient-stimulated GLP-1 secretion, and GLP-1R-deficient mice. We show that the effect of RYGB to enhance glucose-stimulated GLP-1 secretion was greatly attenuated in α-Gust−/− mice. In both genetic models, RYGB reduced body weight and improved glucose homeostasis to levels observed in lean control mice. Therefore, GLP-1, acting through its classical GLP-1R or its bioactive metabolites, does not seem to be involved in the effects of RYGB on body weight and glucose homeostasis.

Taste perception

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Gut hormones

Weight-loss surgery

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Title: Subtitle: Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency
Creators: Mohamad Mokadem - Center for Hypothalamic Research, Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
Juliet F Zechner - Center for Hypothalamic Research, Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
Robert F Margolskee - Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA
Daniel J Drucker - Department of Medicine, Mt. Sinai Hospital, Samuel Lunenfeld Research Institute, University of Toronto, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5
Vincent Aguirre - Center for Hypothalamic Research, Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
Resource Type: Journal article
Publication Details: Molecular metabolism (Germany), Vol.3(2), pp.191-201
DOI: 10.1016/j.molmet.2013.11.010
PMID: 24634822
NLM abbreviation: Mol Metab
ISSN: 2212-8778
eISSN: 2212-8778
Publisher: Elsevier GmbH
Language: English
Date published: 04/2014
Academic Unit: Gastroenterology and Hepatology; Internal Medicine
Record Identifier: 9984094738402771

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