期刊
MOLECULAR METABOLISM
卷 3, 期 2, 页码 191-201出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molmet.2013.11.010
关键词
Weight-loss surgery; Gut hormones; Mouse model; Taste perception
资金
- NIDCD NIH HHS [R01 DC003055] Funding Source: Medline
- NIDDK NIH HHS [T32 DK007745, K08 DK091511, R01 DK081421] Funding Source: Medline
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 ce-gustducin-deficient (alpha-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 alpha-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. (C) 2013 The Authors. Published by Elsevier GmbH.
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