Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes |
| |
Authors: | Valeria Nesca Claudiane Guay Cécile Jacovetti Véronique Menoud Marie-Line Peyot D Ross Laybutt Marc Prentki Romano Regazzi |
| |
Institution: | 1. Department of Fundamental Neurosciences, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 9, CH-1005, Lausanne, Switzerland 2. Molecular Nutrition Unit and the Montreal Diabetes Research Center at the CRCHUM and the Departments of Nutrition and Biochemistry, University of Montreal, Montreal, QC, Canada 3. Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St Vincent’s Hospital, Sydney, NSW, Australia
|
| |
Abstract: | Aims/hypothesis 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 obesity-associated type 2 diabetes and to assess their potential contribution to the development of the disease. Methods MicroRNA profiling of pancreatic islets isolated from prediabetic and diabetic db/db mice and from mice fed a high-fat 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 cells. Results MicroRNAs differentially expressed in both models of obesity-associated type 2 diabetes fall into two distinct categories. A group including miR-132, miR-184 and miR-338-3p 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 miR-34a, miR-146a, miR-199a-3p, miR-203, miR-210 and miR-383 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 insulin-secreting cells may cause beta cell demise and diabetes manifestation. Conclusions/interpretation We propose that maintenance of blood glucose homeostasis or progression toward glucose intolerance and type 2 diabetes may be determined by the balance between expression changes of particular microRNAs. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|