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ludc web

Lena Eliasson

Principal investigator

ludc web

Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell.

Author

  • Sudhir G Tattikota
  • Thomas Rathjen
  • Sarah J McAnulty
  • Hans-Hermann Wessels
  • Ildem Akerman
  • Martijn van de Bunt
  • Jean Hausser
  • Jonathan Esguerra
  • Anne Musahl
  • Amit K Pandey
  • Xintian You
  • Wei Chen
  • Pedro L Herrera
  • Paul R Johnson
  • Donal O'Carroll
  • Lena Eliasson
  • Mihaela Zavolan
  • Anna L Gloyn
  • Jorge Ferrer
  • Ruby Shalom-Feuerstein
  • Daniel Aberdam
  • Matthew N Poy

Summary, in English

Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2014

Language

English

Pages

122-134

Publication/Series

Cell Metabolism

Volume

19

Issue

1

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1550-4131