Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes.

Détails

Ressource 1Télécharger: BIB_0B2D0383973F.P001.pdf (1146.10 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_0B2D0383973F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes.
Périodique
Diabetologia
Auteur(s)
Nesca V., Guay C., Jacovetti C., Menoud V., Peyot M.L., Laybutt D.R., Prentki M., Regazzi R.
ISSN
1432-0428 (Electronic)
ISSN-L
0012-186X
Statut éditorial
Publié
Date de publication
2013
Volume
56
Numéro
10
Pages
2203-2212
Langue
anglais
Résumé
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.
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/09/2013 19:40
Dernière modification de la notice
20/08/2019 13:32
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