title: Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Fundamental Neurosciences, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland.
authors.forename: Valeria
authors.initials: V
authors.lastname: Nesca
authors.forename: Claudiane
authors.initials: C
authors.lastname: Guay
authors.forename: Cécile
authors.initials: C
authors.lastname: Jacovetti
authors.forename: Véronique
authors.initials: V
authors.lastname: Menoud
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Peyot
authors.forename: D Ross
authors.initials: DR
authors.lastname: Laybutt
authors.forename: Marc
authors.initials: M
authors.lastname: Prentki
authors.forename: Romano
authors.initials: R
authors.lastname: Regazzi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007515:Islets of Langerhans / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D035683:MicroRNAs