The long-chain fatty acid receptor, GPR40, and glucolipotoxicity: investigations using GPR40-knockout mice
The long-chain fatty acid receptor, GPR40, and glucolipotoxicity: investigations using GPR40-knockout mice
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DOI：
10.1042/bst0360950
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发表时间：
2008-10-01
影响因子：
3.9
通讯作者：
Smith, David M.
中科院分区：
文献类型：
--
作者：
Brownlie, Ruth;Mayers, Rachel M.;Smith, David M.
GPR40(G蛋白偶联受体40)是一种与长链脂肪酸相关的生理受体。它是一种A家族G蛋白偶联受体，在β细胞中高度表达，它通过G(Q)和磷脂酶C信号增加胰岛素的分泌。众所周知，脂肪酸对β细胞既有急性刺激效应，也有慢性有害效应。GPR40转基因动物和GPR40(-/-)动物已成为研究GPR40代谢效应的重要工具。在本文中，我们回顾了转基因GPR40模型的文献，并介绍了我们自己关于高脂饮食对GPR(-/-)小鼠代谢表型影响的一些研究。GPR40配体代表了治疗2型糖尿病的有趣的新疗法，但目前尚不清楚是激动剂还是拮抗剂代表最好的治疗方法。
GPR40 (G-protein-coupled receptor 40) has been shown to be a physiologically relevant receptor for long-chain fatty acids. it is a family A G-protein-coupled receptor highly expressed in the beta-cell where it increases insulin secretion by signalling via G(q) and phospholipase C. Fatty acids are well known to mediate both acute stimulatory effects and chronic detrimental effects on the beta-cell. GPR40-transgenic and GPR40(-/-) animals have been important tools in studies of the metabolic effects of GPR40. In the present article, we review the literature on transgenic GPR40 models and present some of our own studies on the effects of a high-fat diet on the metabolic phenotype of GPR(-/-) mice. GPR40 ligands represent interesting novel therapies for Type 2 diabetes but it is presently unclear whether agonists or antagonists represent the best therapeutic approach.