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A pancreatic islet-specific microRNA regulates insulin secretion

Author

Listed:
  • 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
    University of Oxford, Churchill Hospital)

  • Markus Stoffel

    (The Rockefeller University)

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.

Suggested Citation

  • Matthew N. Poy & Lena Eliasson & Jan Krutzfeldt & Satoru Kuwajima & Xiaosong Ma & Patrick E. MacDonald & Sébastien Pfeffer & Thomas Tuschl & Nikolaus Rajewsky & Patrik Rorsman & Markus Stoffel, 2004. "A pancreatic islet-specific microRNA regulates insulin secretion," Nature, Nature, vol. 432(7014), pages 226-230, November.
    • Handle: RePEc:nat:nature:v:432:y:2004:i:7014:d:10.1038_nature03076
    DOI: 10.1038/nature03076
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    Cited by:

    1. Julian Krauskopf & Theo M de Kok & Shelli J Schomaker & Mark Gosink & Deborah A Burt & Patricia Chandler & Roscoe L Warner & Kent J Johnson & Florian Caiment & Jos C Kleinjans & Jiri Aubrecht, 2017. "Serum microRNA signatures as "liquid biopsies" for interrogating hepatotoxic mechanisms and liver pathogenesis in human," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-17, May.
    2. Thuc Duy Le & Junpeng Zhang & Lin Liu & Jiuyong Li, 2015. "Ensemble Methods for MiRNA Target Prediction from Expression Data," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-19, June.
    3. Ajoy Mallik & Nripendranath Mandal, 2014. "Bibliometric analysis of global publication output and collaboration structure study in microRNA research," Scientometrics, Springer;Akadémiai Kiadó, vol. 98(3), pages 2011-2037, March.
    4. Alexander Link & Verena Becker & Ajay Goel & Thomas Wex & Peter Malfertheiner, 2012. "Feasibility of Fecal MicroRNAs as Novel Biomarkers for Pancreatic Cancer," PLOS ONE, Public Library of Science, vol. 7(8), pages 1-9, August.

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