A pancreatic islet-specific microRNA regulates insulin secretion

Poy, Matthew N; Eliasson, Lena; Krutzfeldt, Jan; Kuwajima, Satoru; Ma, Xiaosong; Macdonald, Patrick E; Pfeffer, Sébastien; Tuschl, Thomas; Rajewsky, Nikolaus; Rorsman, Patrik; Stoffel, Markus (2004). A pancreatic islet-specific microRNA regulates insulin secretion. Nature, 432(7014), pp. 226-30. London: Macmillan Journals Ltd. 10.1038/nature03076

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Endocrinology, Diabetology and Clinical Nutrition

UniBE Contributor:

Krützfeldt, Jan

ISSN:

0028-0836

ISBN:

15538371

Publisher:

Macmillan Journals Ltd.

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:06

Last Modified:

04 May 2014 23:20

Publisher DOI:

10.1038/nature03076

PubMed ID:

15538371

Web of Science ID:

000225020200048

URI:

https://boris.unibe.ch/id/eprint/28595 (FactScience: 121983)

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