A pancreatic islet-specific microRNA regulates insulin secretion.

Journal article

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.

Authors: Poy, M; Eliasson, L; Krutzfeldt, J; Kuwajima, S; Ma, X

• Publication status: Published
• Journal: Nature
• Volume: 432
• Issue: 7014
• Pages: 226-230
• Publication date: 2004-11-01
• DOI: 10.1038/nature03076
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: MicroRNAs; Glucose; Animals; Diabetes Mellitus; Insulin; Cloning, Molecular; Potassium Chloride; Substrate Specificity; Islets of Langerhans; Genetic Therapy; Calcium Signaling; Exocytosis; Cell Line; Organ Specificity; Gene Expression; Mice; Tolbutamide; Intercellular Signaling Peptides and Proteins; Gene Silencing