Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2006 Jan 27;339(4):1063-8. Epub 2005 Dec 1.

Notch signaling: a mediator of beta-cell de-differentiation in diabetes?

Author information

1
Laboratory of Experimental Medicine, Université Libre de Bruxelles, Belgium. mdarvill@ulb.ac.be

Abstract

Cytokines are mediators of pancreatic beta-cell dysfunction and death in type 1 diabetes mellitus. Microarray analyses of insulin-producing cells exposed to interleukin-1beta+interferon-gamma showed decreased expression of genes related to beta-cell-differentiated functions and increased expression of members of the Notch signaling pathway. Re-expression of this developmental pathway may contribute for loss-of-function of beta-cells exposed to an autoimmune attack. In this study, we show that rat primary beta-cells exposed to cytokines up-regulate several Notch receptors and ligands, and the target gene Hes1. Transfection of insulin-producing INS-1E cells and primary rat beta-cells with a constitutively active form of the Notch receptor down-regulated Pdx1 and insulin expression in INS-1E cells but not in primary beta-cells. Thus, activation of the Notch pathway inhibits differentiated functions in dividing but not in terminally differentiated beta-cells.

PMID:
16337608
DOI:
10.1016/j.bbrc.2005.11.111
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center