Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 2326282
Author(s) 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 L; Johnson, Paul R; O'Carroll, Donal; Eliasson, Lena; Zavolan, Mihaela; Gloyn, Anna L; Ferrer, Jorge; Shalom-Feuerstein, Ruby; Aberdam, Daniel; Poy, Matthew N
Author(s) at UniBasel Zavolan, Mihaela
Hausser, Jean
Year 2013
Title Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell
Journal Cell metabolism
Volume 19
Number 1
Pages / Article-Number 122-34

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.

Publisher Cell Press
ISSN/ISBN 1550-4131
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.cmet.2013.11.015
PubMed ID
ISI-Number WOS:000329431200014
Document type (ISI) Journal Article

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