Diabetes Research Today is a free monthly online journal that collates and summarizes the latest research about Diabetes, including details on insulin, type i, type ii, diet, treatment, prevention.

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

Darville MI, Eizirik DL

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

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.

Published 19 December 2005 in Biochem Biophys Res Commun, 339(4): 1063-8.
Full-text of this article is available online (may require subscription).

© 2004-2008 Diabetes Research Today. All Rights Reserved.