g 蛋白偶联受体40 研究进展research progress in g protein - 生物通.pdfVIP

HEREDITAS (Beijing) 2012 年*月, 34(*): ISSN 0253-9772 G 蛋白偶联受体40 研究进展 武珅,陆涛峰,武爽,关伟军 中国农业科学院北京畜牧兽医研究所,北京100193 摘要：G 蛋白偶联受体40 （G protein-coupled receptor 40, GPR40 ）是一种具有7 个跨膜α 螺旋结构的G 蛋 白偶联受体，主要分布于胰腺细胞和神经系统细胞。它能与机体内游离的中长链脂肪酸结合，激活细胞内 信号通路，从而调节其生理功能。在胰岛细胞中，GPR40 可被游离脂肪酸激活，促使细胞内钙离子浓度升 高，进而促进胰岛素释放。根据这一机理，以GPR40 为靶点的激动剂类药物相继被开发，用于糖尿病治疗。 GPR40 也参与神经发生过程，但到目前为止其相关机制尚不清楚。文章从基因结构、表达调控、蛋白配体 及应用、生理功能等方面详细介绍了GPR40 的研究现状，总结了目前研究中所遇到的问题，并对未来的研 究热点进行展望。 关键词：GPR40 ；中长链脂肪酸；胰岛素分泌；神经发生；味觉 Research progress in G protein-coupled receptor 40 WU Shen, LU Tao-Feng, WU Shuang, GUAN Wei-Jun Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193，China Abstract: GPR40 is one of the G protein-coupled receptors, which has 7 transmembrance spanning helical bundles. GPR40 distributes in pancreas and central nervous system. It can be bound by medium and long chain fatty acid and activate the intracellular signal pathways, which in turn regulates the function of cells. In β-cell, intracellular calcium concentration elevates when GPR40 is binding to fatty acid, thereby promoting the release of insulin. According to the theory, new drugs, the agonist of GPR40, have been used for prepreventing and treating the diabetas. In the nervous system, GPR40 is involved in neurogenesis, but the mechanism how GPR40 works is unclear until now. In thisreview, the research progressof GPR40 was reviewed, especially about the structure and characteristics of GPR40 gene, ligands and function. We focused on the problems encountered in the current research and the hot points in the future. Keywords: GPR40; medium and long chain fatty acid; insulin secret; neurogenesis; gustation G 蛋白偶联受体（G-protein couple receptors, GPCRs ），又称为7α 螺旋跨膜受体蛋白 （Seven α-helices transmembrance segment receptor, 7TM receptor ），是体内最大的蛋白质超家 族。迄今为止已有大量GPCRs 被发现，虽然他们的序列同源性较低，但在结构上都具有7 收稿日期：2012-06-30 ；修回日期：2012-08-15 基金项目：转基因生物新品种培育科技重大专项 （编号：2011ZX08009-003-006 ）