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Article scientifique
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Argonaute2 mediates compensatory expansion of the pancreatic β cell

Publié dansCell metabolism, vol. 19, no. 1, p. 122-134
Date de publication2014
Résumé

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.

Mots-clés
  • 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 (format ISO)
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
Fichiers principaux (1)
Article (Published version)
accessLevelPublic
Identifiants
ISSN du journal1550-4131
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Informations techniques

Création09/04/2015 14:57:00
Première validation09/04/2015 14:57:00
Heure de mise à jour14/03/2023 23:10:37
Changement de statut14/03/2023 23:10:36
Dernière indexation16/01/2024 17:43:51
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