@article{Tattikota:2014:10.1016/j.cmet.2013.11.015,
author = {Tattikota, SG and Rathjen, T and McAnulty, SJ and Wessels, H-H and Akerman, I and van, de Bunt M and Hausser, J and Esguerra, JLS and Musahl, A and Pandey, AK and You, X and Chen, W and Herrera, PL and Johnson, PR and O'Carroll, D and Eliasson, L and Zavolan, M and Gloyn, AL and Ferrer, J and Shalom-Feuerstein, R and Aberdam, D and Poy, MN},
doi = {10.1016/j.cmet.2013.11.015},
journal = {Cell Metabolism},
pages = {122--134},
title = {Argonaute2 mediates compensatory expansion of the pancreatic beta cell},
url = {http://dx.doi.org/10.1016/j.cmet.2013.11.015},
volume = {19},
year = {2014}
}

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TY  - JOUR
AB  - 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.
AU  - Tattikota,SG
AU  - Rathjen,T
AU  - McAnulty,SJ
AU  - Wessels,H-H
AU  - Akerman,I
AU  - van,de Bunt M
AU  - Hausser,J
AU  - Esguerra,JLS
AU  - Musahl,A
AU  - Pandey,AK
AU  - You,X
AU  - Chen,W
AU  - Herrera,PL
AU  - Johnson,PR
AU  - O'Carroll,D
AU  - Eliasson,L
AU  - Zavolan,M
AU  - Gloyn,AL
AU  - Ferrer,J
AU  - Shalom-Feuerstein,R
AU  - Aberdam,D
AU  - Poy,MN
DO  - 10.1016/j.cmet.2013.11.015
EP  - 134
PY  - 2014///
SN  - 1932-7420
SP  - 122
TI  - Argonaute2 mediates compensatory expansion of the pancreatic beta cell
T2  - Cell Metabolism
UR  - http://dx.doi.org/10.1016/j.cmet.2013.11.015
UR  - http://hdl.handle.net/10044/1/38934
VL  - 19
ER  - 

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