A pancreatic islet-specific microRNA regulates insulin secretion

Matthew N. Poy, Lena Eliasson, Jan Krutzfeldt, Satoru Kuwajima, Xiaosong Ma, Patrick E. MacDonald, Sébastien Pfeffer, Thomas Tuschl, Nikolaus Rajewsky, Patrick Rorsman, Markus Stoffel

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression1. Several miRNAs in animals exhibit tissue-specific or developmental-stage- specific expression, indicating that they could play important roles in many biological processes2-4. 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.

Original languageEnglish (US)
Pages (from-to)226-230
Number of pages5
JournalNature
Volume432
Issue number7014
DOIs
StatePublished - Nov 11 2004
Externally publishedYes

ASJC Scopus subject areas

  • General

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