环磷酸腺苷（cAMP）通过CREB介导的胰岛素受体底物2（IRS2）诱导作用促进胰腺β细胞存活。
cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2.
作者信息
Jhala Ulupi S, Canettieri Gianluca, Screaton Robert A, Kulkarni Rohit N, Krajewski Stan, Reed John, Walker John, Lin Xueying, White Morris, Montminy Marc
机构信息
The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
出版信息
Genes Dev. 2003 Jul 1;17(13):1575-80. doi: 10.1101/gad.1097103.
Abstract
The incretin hormone GLP1 promotes islet-cell survival via the second messenger cAMP. Here we show that mice deficient in the activity of CREB, caused by expression of a dominant-negative A-CREB transgene in pancreatic beta-cells, develop diabetes secondary to beta-cell apoptosis. Remarkably, A-CREB severely disrupted expression of IRS2, an insulin signaling pathway component that is shown here to be a direct target for CREB action in vivo. As induction of IRS2by cAMP enhanced activation of the survival kinase Akt in response to insulin and IGF-1, our results demonstrate a novel mechanism by which opposing pathways cooperate in promoting cell survival.
摘要
肠促胰岛素激素胰高血糖素样肽-1（GLP1）通过第二信使环磷酸腺苷（cAMP）促进胰岛细胞存活。我们在此表明，由于在胰腺β细胞中表达显性负性A-CREB转基因而导致CREB活性缺乏的小鼠，会因β细胞凋亡而继发糖尿病。值得注意的是，A-CREB严重破坏了胰岛素受体底物2（IRS2）的表达，IRS2是胰岛素信号通路的一个组成部分，在此被证明是CREB在体内作用的直接靶点。由于cAMP诱导IRS2可增强存活激酶Akt对胰岛素和胰岛素样生长因子-1（IGF-1）的反应性激活，我们的结果证明了一种新机制，即相反的信号通路协同促进细胞存活。
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