par Darville, Martine 
;Eizirik, Decio L.
Référence Biochemical and biophysical research communications, 339, 4, page (1063-1068)
Publication Publié, 2006
;Eizirik, Decio L. Référence Biochemical and biophysical research communications, 339, 4, page (1063-1068)
Publication Publié, 2006
Article révisé par les pairs
| Résumé : | 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. |
