GLP-1 protects beta-cells against apoptosis by enhancing the activity of an IGF-2/IGF-1 receptor autocrine loop

Details

Serval ID
serval:BIB_3E5801696B4F
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
GLP-1 protects beta-cells against apoptosis by enhancing the activity of an IGF-2/IGF-1 receptor autocrine loop
Journal
Islets
Author(s)
Cornu M, Thorens B
ISSN
1938-2014
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
1
Number
3
Pages
280-282
Language
english
Abstract
GLP-1 protects β-cells against apoptosis by still incompletely understood mechanisms. In a recent study, we searched for novel anti-apoptotic pathways by performing comparative transcriptomic analysis of islets from Gipr-/-;Glp-1r-/- mice, which show increased susceptibility to cytokine-induced apoptosis. We observed a strong reduction in IGF-1R expression in the knockout islets suggesting a link between the gluco-incretin and IGF-1R signaling pathways. Using MIN6 and primary islet cells, we demonstrated that GLP-1 strongly stimulates IGF-1R expression and that activation of the IGF-1R/Akt signaling pathway required active secretion of IGF-2 by the β-cells. We showed that inactivation of the IGF-1 receptor gene in β-cells or preventing its up-regulation by GLP-1, as well as suppressing IGF-2 expression or action, blocked the protective effect of GLP-1 against cytokine-induced apoptosis. Thus, an IGF-2/IGF-1 receptor autocrine loop operates in β-cells and GLP-1 increases its activity by enhancing IGF-1R expression and by stimulating IGF-2 secretion. This mechanism is required for GLP-1 to protect β-cells against apoptosis.
Keywords
islets, GLP-1, IGF-2, IGF1-R, apoptosis, b-cells
Web of science
Create date
01/02/2010 12:52
Last modification date
20/08/2019 13:35
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