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Argonaute2 mediates compensatory expansion of the pancreatic β cell |
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Published in | Cell metabolism. 2014, vol. 19, no. 1, p. 122-34 | |
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 | |
Identifiers | PMID: 24361012 | |
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Research group | Types cellulaires pancréatiques pendant l'ontogénèse (522) | |
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. 122-34. doi: 10.1016/j.cmet.2013.11.015 https://archive-ouverte.unige.ch/unige:55459 |