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, Patrik Rorsman and Markus Stoffel ()
Additional contact information
Matthew N. Poy: The Rockefeller University
Lena Eliasson: Lund University
Jan Krutzfeldt: The Rockefeller University
Satoru Kuwajima: The Rockefeller University
Xiaosong Ma: Lund University
Patrick E. MacDonald: Lund University
Sébastien Pfeffer: The Rockefeller University
Thomas Tuschl: The Rockefeller University
Nikolaus Rajewsky: New York University
Patrik Rorsman: Lund University
Markus Stoffel: The Rockefeller University

Nature, 2004, vol. 432, issue 7014, 226-230

Abstract: 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 processes2,3,4. 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.

Date: 2004
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/nature03076 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:432:y:2004:i:7014:d:10.1038_nature03076

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature03076

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().