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- Title
A pancreatic islet-specific microRNA regulates insulin secretion.
- Authors
Poy, Matthew N; Eliasson, Lena; Krutzfeldt, Jan; Kuwajima, Satoru; Ma, Xiaosong; Macdonald, Patrick E; Pfeffer, Sébastien; Tuschl, Thomas; Rajewsky, Nikolaus; Rorsman, Patrik; Stoffel, Markus
- 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.
- Publication
Nature, 2004, Vol 432, Issue 7014, p226
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature03076