Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells

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.