Argonaute2 mediates compensatory expansion of the pancreatic β cell.

Journal article

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.

Authors: Tattikota, S; Rathjen, T; McAnulty, S; Wessels, H; Akerman, I

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell metabolism
• Volume: 19
• Issue: 1
• Pages: 122-134
• Publication date: 2014-01-01
• DOI: 10.1016/j.cmet.2013.11.015
• EISSN: 1932-7420
• ISSN: 1550-4131
• Language: English
• Keywords: Animals; Argonaute Proteins; MicroRNAs; Gene Silencing; Insulin-Secreting Cells; Mice, Obese; Humans; Gene Expression Regulation; Ketogenic Diet; Insulin Resistance; Cell Proliferation; Mice