en
Scientific article
Open access
English

Argonaute2 mediates compensatory expansion of the pancreatic β cell

Published inCell metabolism, vol. 19, no. 1, p. 122-134
Publication date2014
Abstract

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.

Keywords
  • Animals
  • Argonaute Proteins/metabolism
  • Cell Proliferation
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Insulin Resistance/genetics
  • Insulin-Secreting Cells/cytology/metabolism
  • Ketogenic Diet
  • Mice
  • Mice, Obese
  • MicroRNAs/genetics/metabolism
Citation (ISO format)
TATTIKOTA, Sudhir G et al. Argonaute2 mediates compensatory expansion of the pancreatic β cell. In: Cell metabolism, 2014, vol. 19, n° 1, p. 122–134. doi: 10.1016/j.cmet.2013.11.015
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal1550-4131
525views
447downloads

Technical informations

Creation04/09/2015 2:57:00 PM
First validation04/09/2015 2:57:00 PM
Update time03/14/2023 11:10:37 PM
Status update03/14/2023 11:10:36 PM
Last indexation01/16/2024 5:43:51 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack