Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiencya,b
Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiencya,b
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DOI：
10.1016/j.molmet.2013.11.010
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发表时间：
2014-04-01
影响因子：
8.1
通讯作者：
Aguirre, Vincent
中科院分区：
文献类型：
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作者：
Mokadem, Mohamad;Zechner, Juliet F.;Aguirre, Vincent
胰高血糖素样肽-1（GLP-1）的分泌在Roux-en-Y胃旁路术（RYGB）后大大增强。虽然完整的GLP-1通过经典GLP-1受体（GLP-1 R）发挥其代谢作用，但循环GLP-1的蛋白水解加工产生代谢产物，如GLP-1（9-36）酰胺/GLP-1（28-36）酰胺，其发挥与经典GLP-1 R无关的类似作用。我们使用两种功能性GLP-1缺陷型ce-gustducin缺陷（α-Gust（-/-））小鼠模型（表现出营养刺激的GLP-1分泌减弱）和GLP-1 R缺陷型小鼠模型，研究了GLP-1通过这些代谢物或其已知受体发挥作用是RYGB有益作用所必需的假设。我们发现，RYGB增强葡萄糖刺激的GLP-1分泌的作用在α-Gust（-/-）小鼠中大大减弱。在这两种遗传模型中，RYGB降低了体重，改善了葡萄糖稳态，达到了瘦对照小鼠的水平。因此，GLP-1通过其经典GLP-1 R或其生物活性代谢产物起作用，似乎不参与RYGB对体重和葡萄糖稳态的影响。(C)2013作者由爱思唯尔有限公司出版。
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.