First Author | Mohan R | Year | 2015 |
Journal | J Biol Chem | Volume | 290 |
Issue | 32 | Pages | 19955-66 |
PubMed ID | 26109062 | Mgi Jnum | J:345363 |
Mgi Id | MGI:6838739 | Doi | 10.1074/jbc.M115.650705 |
Citation | Mohan R, et al. (2015) Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic beta- and alpha-Cells. J Biol Chem 290(32):19955-66 |
abstractText | Insulin secreted from pancreatic beta-cells and glucagon secreted from pancreatic alpha-cells are the two major hormones working in the pancreas in an opposing manner to regulate and maintain a normal glucose homeostasis. How microRNAs (miRNAs), a population of non-coding RNAs so far demonstrated to be differentially expressed in various types of cells, regulate gene expression in pancreatic beta-cells and its closely associated alpha-cells is not completely clear. In this study, miRNA profiling was performed and compared between pancreatic beta-cells and their partner alpha-cells. One novel miRNA, miR-483, was identified for its highly differential expression in pancreatic beta-cells when compared to its expression in alpha-cells. Overexpression of miR-483 in beta-cells increased insulin transcription and secretion by targeting SOCS3, a member of suppressor of cytokine signaling family. In contrast, overexpression of miR-483 decreased glucagon transcription and secretion in alpha-cells. Moreover, overexpressed miR-483 protected against proinflammatory cytokine-induced apoptosis in beta-cells. This correlates with a higher expression level of miR-483 and the expanded beta-cell mass observed in the islets of prediabetic db/db mice. Together, our data suggest that miR-483 has opposite effects in alpha- and beta-cells by targeting SOCS3, and the imbalance of miR-483 and its targets may play a crucial role in diabetes pathogenesis. |