Authors: Valeria Nesca Claudiane Guay Cécile Jacovetti Véronique Menoud MarieLine Peyot D Ross Laybutt Marc Prentki Romano Regazzi
Publish Date: 2013/07/11
Volume: 56, Issue: 10, Pages: 2203-2212
Abstract
MicroRNAs are key regulators of gene expression involved in health and disease The goal of our study was to investigate the global changes in beta cell microRNA expression occurring in two models of obesityassociated type 2 diabetes and to assess their potential contribution to the development of the diseaseMicroRNA profiling of pancreatic islets isolated from prediabetic and diabetic db/db mice and from mice fed a highfat diet was performed by microarray The functional impact of the changes in microRNA expression was assessed by reproducing them in vitro in primary rat and human beta cellsMicroRNAs differentially expressed in both models of obesityassociated type 2 diabetes fall into two distinct categories A group including miR132 miR184 and miR3383p displays expression changes occurring long before the onset of diabetes Functional studies indicate that these expression changes have positive effects on beta cell activities and mass In contrast modifications in the levels of miR34a miR146a miR199a3p miR203 miR210 and miR383 primarily occur in diabetic mice and result in increased beta cell apoptosis These results indicate that obesity and insulin resistance trigger adaptations in the levels of particular microRNAs to allow sustained beta cell function and that additional microRNA deregulation negatively impacting on insulinsecreting cells may cause beta cell demise and diabetes manifestation
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