| First Author | Poy MN | Year | 2004 |
| Journal | Nature | Volume | 432 |
| Issue | 7014 | Pages | 226-30 |
| PubMed ID | 15538371 | Mgi Jnum | J:94160 |
| Mgi Id | MGI:3511399 | Doi | 10.1038/nature03076 |
| Citation | Poy MN, et al. (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432(7014):226-30 |
| abstractText | MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression. Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes. To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion. The mechanism by which secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si)RNA mimicked the effects of miR-375 on glucose-stimulated insulin secretion and exocytosis. Thus, miR-375 is a regulator of insulin secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes. |
