| Literature DB >> 12842910 |
Ulupi S Jhala1, Gianluca Canettieri, Robert A Screaton, Rohit N Kulkarni, Stan Krajewski, John Reed, John Walker, Xueying Lin, Morris White, Marc Montminy.
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.Entities:
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Year: 2003 PMID： 12842910 PMCID： PMC196130 DOI： 10.1101/gad.1097103
Source DB: PubMed Journal: Genes Dev ISSN： 0890-9369 Impact factor: 11.361