Format

Send to

Choose Destination
Genes Dev. 2003 Jul 1;17(13):1575-80.

cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2.

Author information

1
The Salk Institute for Biological Studies, La Jolla, California 92037, USA.

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.

PMID:
12842910
PMCID:
PMC196130
DOI:
10.1101/gad.1097103
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center