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A pancreatic islet-specific microRNA regulates insulin secretion

Item Type:Article
Title:A pancreatic islet-specific microRNA regulates insulin secretion
Creators Name:Poy, M.N. and Eliasson, L. and Krutzfeldt, J. and Kuwajima, S. and Ma, X. and Macdonald, P.E. and Pfeffer, S. and Tuschl, T. and Rajewsky, N. and Rorsman, P. and Stoffel, M.
Abstract: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.
Keywords:Calcium Signaling, Cell Line, Molecular Cloning, Diabetes Mellitus, Exocytosis, Gene Expression, Gene Silencing, Gene Therapy, Glucose, Insulin, Intercellular Signaling Peptides and Proteins, Islets of Langerhans, MicroRNAs, Organ Specificity, Potassium Chloride, Substrate Specificity, Tolbutamide, Animals, Mice
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:432
Number:7014
Page Range:226-230
Date:11 November 2004
Official Publication:https://doi.org/10.1038/nature03076
PubMed:View item in PubMed

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