cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2.
cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2.
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发表时间：
2003
影响因子：
10.5
通讯作者：
U. Jhala;G. Canettieri;R. Screaton;R. Kulkarni;S. Krajewski;J. Reed;John Walker;Xueying Lin
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文献类型：
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作者：
U. Jhala;G. Canettieri;R. Screaton;R. Kulkarni;S. Krajewski;J. Reed;John Walker;Xueying Lin
肠促胰岛素激素GLP 1通过第二信使cAMP促进胰岛细胞存活。在这里，我们表明，小鼠缺乏CREB的活性，引起的显性负A-CREB转基因在胰腺β细胞的表达，发展糖尿病继发于β细胞凋亡。值得注意的是，A-CREB严重破坏IRS 2的表达，IRS 2是一种胰岛素信号传导途径组分，在此显示为CREB体内作用的直接靶标。由于cAMP诱导IRS 2增强了存活激酶Akt对胰岛素和IGF-1的响应，我们的研究结果证明了一种新的机制，通过这种机制，对立的通路合作促进细胞存活。
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.