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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
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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 AnimalsArgonaute Proteins/metabolismCell ProliferationGene Expression RegulationGene SilencingHumansInsulin Resistance/geneticsInsulin-Secreting Cells/cytology/metabolismKetogenic DietMiceMice, ObeseMicroRNAs/genetics/metabolism
Identifiers
PMID: 24361012
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Article (Published version) (1.5 MB) - public document Free access
Structures
Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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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

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Deposited on : 2015-04-13

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