Argonaute2 mediates compensatory expansion of the pancreatic β cell

Tattikota, Sudhir G; Rathjen, Thomas; McAnulty, Sarah J; Wessels, Hans-Hermann; Akerman, Ildem; van de Bunt, Martijn; Hausser, Jean; Esguerra, Jonathan L S; Musahl, Anne; Pandey, Amit K; You, Xintian; Chen, Wei; Herrera, Pedro Luis; Johnson, Paul R; O'Carroll, Donal; Eliasson, Lena; Zavolan, Mihaela; Gloyn, Anna L; Ferrer, Jorge; Shalom-Feuerstein, Ruby; Aberdam, Daniel; Poy, Matthew N

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Title		Argonaute2 mediates compensatory expansion of the pancreatic β cell
Authors		Tattikota, Sudhir G Rathjen, Thomas McAnulty, Sarah J Wessels, Hans-Hermann Akerman, Ildem van de Bunt, Martijn Hausser, Jean Esguerra, Jonathan L S Musahl, Anne Pandey, Amit K You, Xintian Chen, Wei Herrera, Pedro Luis Johnson, Paul R O'Carroll, Donal Eliasson, Lena Zavolan, Mihaela Gloyn, Anna L Ferrer, Jorge Shalom-Feuerstein, Ruby Aberdam, Daniel Poy, Matthew N show all authors [1 - 22]
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		DOI: 10.1016/j.cmet.2013.11.015 PMID: 24361012
Full text		Article (Published version) (1.5 MB) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
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. https://archive-ouverte.unige.ch/unige:55459