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

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Jhala US,Canettieri G,Screaton RA,Kulkarni RN,Krajewski S,Reed J,Walker J,Lin X,White M,Montminy M

doi

10.1101/gad.1097103

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

1575-80

issue

13

eissn

0890-9369

issn

1549-5477

pii

17/13/1575

journal_volume

17

pub_type

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