Argonaute2 mediates compensatory expansion of the pancreatic β cell

Sudhir G Tattikota, Thomas Rathjen, Sarah J McAnulty, Hans-Hermann Wessels, Ildem Akerman, Martijn van de Bunt, Jean Hausser, Jonathan L S 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-FeuersteinDaniel Aberdam, Matthew N Poy

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)122-34
Number of pages13
JournalCell Metabolism
Issue number1
Early online date19 Dec 2013
Publication statusPublished - 7 Jan 2014


  • Animals
  • Argonaute Proteins
  • Cell Proliferation
  • Diet, Ketogenic
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Insulin Resistance
  • Insulin-Secreting Cells
  • Mice
  • Mice, Obese
  • MicroRNAs
  • Journal Article
  • Research Support, Non-U.S. Gov't


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