胰高血糖素样肽1类似物调节胰岛素分泌细胞增殖和功能的细胞信号通路研究进展  

Progress in signal transduction of glucagon-like peptide 1 on regulating insulin-secreting cell mass and function

作　　者：郭莉霞[1] 刘建辉[1] 陈刚[1] 邓小红[1] 

机构地区：[1]重庆工商大学药物化学与化学生物学研究中心,重庆400067

出　　处：《中国药理学与毒理学杂志》2009年第4期308-311,共4页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30600813);教育部新世纪优秀人才支持计划资助项目(NCET-07-0913)~~

摘　　要：胰岛素分泌细胞的功能紊乱是糖尿病早期的病理学特征。胰高血糖素样肽1(GLP1)是由肠黏膜L细胞分泌和葡萄糖浓度依赖的多肽类激素,它能够刺激胰岛素的基因表达、蛋白质合成和分泌;最重要的是,GLP1作为一种生长因子,可促进胰岛素分泌细胞增殖,并抑制其凋亡,增加其数量,增强其功能。其机制包括多条胞内信号通路,如通过激活GLP1受体激活蛋白激酶A和直接被cAMP活化的交换蛋白,或通过GLP1受体由表皮生长因子β细胞素(β-cellulin)或基质金属蛋白酶反式激活表皮生长因子受体并增加Wnt信号通路因子等。本文综述了近年来GLP1及其类似物调节胰岛素分泌细胞增殖和功能信号通路的研究进展。Dysfunction of insulin-secreting cells is an early pathophysiologieal defect in type 2 diabetes mellitus. Glucagon-like peptide 1 （GLP1） is an ineretin hormone displaying glucose-dependent stimulation of insulin gene expression, biosynthesis and secretion, trophie effects on the insulin-secreting cells, and inhibitory effects on gastrointestinal motility. Furthermore, GLP1 acts as a growth factor by promoting insulin-secreting cell survival and proliferation, and inhibiting of insulin- secreting cell apoptosis. These effects of GLP1 appear to involve multiple intraeellular pathways, including GLP1 receptor-mediated the stimulation of protein kinase A and exchange protein directly activated by cAMP, or GLP1 receptor-mediated transactivation of epidermal growth factor receptor via epidermal growth factor β-cellulin and metalloproteinases, or GLP1 receptor- mediated enhancement of Wnt signaling. This paper summerizes the progress in the molecular mechanisms by which GLP1 signaling induces insulin-secreting cell mass expansion and function.

关 键 词：胰高血糖素样肽1 胰岛素分泌细胞 细胞增殖 信号传导 

分 类 号：R587.1[医药卫生—内分泌]