Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes?
Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes?
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DOI：
10.1152/ajpendo.00137.2010
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发表时间：
2010-07-01
影响因子：
5.1
通讯作者：
Knop, Filip K.
中科院分区：
文献类型：
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作者：
Knop, Filip K.
诺普足球俱乐部胆汁诱导的胰高血糖素样肽-1分泌：2型糖尿病的病理生理学意义？Am J Physiol Endocrinol Metab 299：E10-E13，2010.首次发表于2010年4月27日; doi：10.1152/ajpendo.00137.2010.-在过去的几十年中，已经清楚的是，胆汁酸不仅作为简单的脂肪增溶剂，而且还代表复杂的激素代谢整合剂。胆汁酸激活核受体（控制参与例如胆汁酸、胆固醇和葡萄糖代谢的基因的转录）和细胞表面G蛋白偶联受体TGR 5（调节棕色脂肪和肌肉细胞中的能量消耗）。已经显示TGR 5在肠内分泌L细胞中表达，所述肠内分泌L细胞分泌有效的降糖肠促胰岛素激素胰高血糖素样肽-1（GLP-1）。最近显示胆汁酸诱导的TGR 5活化导致GLP-1的肠分泌，并且增强的TGR 5信号传导改善饮食诱导的肥胖小鼠的餐后葡萄糖耐量。这篇观点文章介绍了这些新的发现，在营养素诱导的GLP-1分泌的背景下，并概述了胆汁酸诱导的GLP-1分泌在生理学，病理生理学和药理学方面的潜在影响。
Knop FK. Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes? Am J Physiol Endocrinol Metab 299: E10-E13, 2010. First published April 27, 2010; doi:10.1152/ajpendo.00137.2010.-During the last decades it has become clear that bile acids not only act as simple fat solubilizers, but additionally represent complex hormonal metabolic integrators. Bile acids activate both nuclear receptors (controlling transcription of genes involved in for example bile acid, cholesterol, and glucose metabolism) and the cell surface G protein-coupled receptor TGR5 (modulating energy expenditure in brown fat and muscle cells). It has been shown that TGR5 is expressed in enteroendocrine L cells, which secrete the potent glucose-lowering incretin hormone glucagon-like peptide-1 (GLP-1). Recently it was shown that bile acid-induced activation of TGR5 results in intestinal secretion of GLP-1 and that enhanced TGR5 signaling improves postprandial glucose tolerance in diet-induced obese mice. This Perspectives article presents these novel findings in the context of prior studies on nutrient-induced GLP-1 secretion and outlines the potential implications of bile acid-induced GLP-1 secretion in physiological, pathophysiological, and pharmacological perspectives.