CAMP promotes pancreatic β-cell survival via CREB-mediated induction of IRS2

被引:468
作者
Jhala, US
Canettieri, G
Screaton, RA
Kulkarni, RN
Krajewski, S
Reed, J
Walker, J
Lin, XY
White, M
Montminy, M
机构
[1] Salk Inst Biol Studies, La Jolla, CA 92037 USA
[2] Burnham Inst, La Jolla, CA 92037 USA
[3] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA
[4] Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA
关键词
D O I
10.1101/gad.1097103
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 IRS2 by 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.
引用
收藏
页码:1575 / 1580
页数:6
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