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ludc web

Lena Eliasson

Principal investigator

ludc web

A pancreatic islet-specific microRNA regulates insulin secretion

Author

  • MN Poy
  • Lena Eliasson
  • J Krutzfeldt
  • S Kuwajima
  • Xiaosong Ma
  • Patrick MacDonald
  • B Pfeffer
  • T Tuschl
  • N Rajewsky
  • Patrik Rorsman
  • M Stoffel

Summary, in English

MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression(1). Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes(2-4). 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.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • Department of Experimental Medical Science

Publishing year

2004

Language

English

Pages

226-230

Publication/Series

Nature

Volume

432

Issue

7014

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 0028-0836