| First Author | Melkman-Zehavi T | Year | 2011 |
| Journal | EMBO J | Volume | 30 |
| Issue | 5 | Pages | 835-45 |
| PubMed ID | 21285947 | Mgi Jnum | J:170352 |
| Mgi Id | MGI:4946351 | Doi | 10.1038/emboj.2010.361 |
| Citation | Melkman-Zehavi T, et al. (2011) miRNAs control insulin content in pancreatic beta-cells via downregulation of transcriptional repressors. EMBO J 30(5):835-45 |
| abstractText | MicroRNAs (miRNAs) were shown to be important for pancreas development, yet their roles in differentiated beta-cells remain unclear. Here, we show that miRNA inactivation in beta-cells of adult mice results in a striking diabetic phenotype. While islet architecture is intact and differentiation markers are maintained, Dicer1-deficient beta-cells show a dramatic decrease in insulin content and insulin mRNA. As a consequence of the change in insulin content, the animals become diabetic. We provide evidence for involvement of a set of miRNAs in regulating insulin synthesis. The specific knockdown of miR-24, miR-26, miR-182 or miR-148 in cultured beta-cells or in isolated primary islets downregulates insulin promoter activity and insulin mRNA levels. Further, miRNA-dependent regulation of insulin expression is associated with upregulation of transcriptional repressors, including Bhlhe22 and Sox6. Thus, miRNAs in the adult pancreas act in a new network that reinforces insulin expression by reducing the expression of insulin transcriptional repressors. |
