Argonaute2 mediates compensatory expansion of the pancreatic β cell

Tattikota, S.G.; Rathjen, T.; McAnulty, S.J.; Wessels, H.H.; Akerman, I.; van de Bunt, M.; Hausser, J.; Esguerra, J.L.S.; Musahl, A.; Pandey, A.K.; You, X.; Chen, W.; Herrera, P.L.; Johnson, P.R.; O'Carroll, D.; Eliasson, L.; Zavolan, M.; Gloyn, A.L.; Ferrer, J.; Shalom-Feuerstein, R.; Aberdam, D.; Poy, M.N.

Argonaute2 mediates compensatory expansion of the pancreatic β cell

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Item Type:	Article
Title:	Argonaute2 mediates compensatory expansion of the pancreatic β cell
Creators:	Tattikota, S.G., Rathjen, T., McAnulty, S.J., Wessels, H.H. ORCID: https://orcid.org/0000-0001-5551-404X, Akerman, I., van de Bunt, M., Hausser, J., Esguerra, J.L.S., Musahl, A., Pandey, A.K. ORCID: https://orcid.org/0000-0002-8886-1694, You, X., Chen, W. ORCID: https://orcid.org/0000-0003-3263-1627, Herrera, P.L., Johnson, P.R., O'Carroll, D., Eliasson, L., Zavolan, M., Gloyn, A.L., Ferrer, J., Shalom-Feuerstein, R., Aberdam, D. and Poy, M.N. ORCID: https://orcid.org/0000-0002-4904-2426
Abstract:	Pancreatic {beta} cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in {beta} 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 {beta} cell expansion. Loss of Ago2 during insulin resistance blocked {beta} 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 {beta} 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:	Argonaute Proteins, Cell Proliferation, Gene Expression Regulation, Gene Silencing, Insulin Resistance, Insulin-Secreting Cells, Ketogenic Diet, MicroRNAs, Animals, Mice
Source:	Cell Metabolism
ISSN:	1550-4131
Publisher:	Cell Press / Elsevier
Volume:	19
Number:	1
Page Range:	122-134
Date:	7 January 2014
Official Publication:	https://doi.org/10.1016/j.cmet.2013.11.015
PubMed:	View item in PubMed

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