| First Author | Zhu Y | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 9 | Pages | 3194-206 |
| PubMed ID | 23761103 | Mgi Jnum | J:208956 |
| Mgi Id | MGI:5565431 | Doi | 10.2337/db13-0151 |
| Citation | Zhu Y, et al. (2013) MicroRNA-24/MODY gene regulatory pathway mediates pancreatic beta-cell dysfunction. Diabetes 62(9):3194-206 |
| abstractText | Overnutrition and genetics both contribute separately to pancreatic beta-cell dysfunction, but how these factors interact is unclear. This study was aimed at determining whether microRNAs (miRNAs) provide a link between these factors. In this study, miRNA-24 (miR-24) was highly expressed in pancreatic beta-cells and further upregulated in islets from genetic fatty (db/db) or mice fed a high-fat diet, and islets subject to oxidative stress. Overexpression of miR-24 inhibited insulin secretion and beta-cell proliferation, potentially involving 351 downregulated genes. By using bioinformatic analysis combined with luciferase-based promoter activity assays and quantitative real-time PCR assays, we identified two maturity-onset diabetes of the young (MODY) genes as direct targets of miR-24. Silencing either of these MODY genes (Hnf1a and Neurod1) mimicked the cellular phenotype caused by miR-24 overexpression, whereas restoring their expression rescued beta-cell function. Our findings functionally link the miR-24/MODY gene regulatory pathway to the onset of type 2 diabetes and create a novel network between nutrient overload and genetic diabetes via miR-24. |
