IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v432y2004i7014d10.1038_nature03076.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature03076
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature03076?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. 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.
    4. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:432:y:2004:i:7014:d:10.1038_nature03076. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.