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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 LU ; Musahl, Anne and Pandey, Amit K, et al. (2014) In Cell Metabolism 19(1). p.122-134
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... (More)
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. (Less)
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published
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Cell Metabolism
volume
19
issue
1
pages
122 - 134
publisher
Cell Press
external identifiers
  • wos:000329431200014
  • pmid:24361012
  • scopus:84891867862
ISSN
1550-4131
DOI
10.1016/j.cmet.2013.11.015
language
English
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yes
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98e5f289-e270-4fe1-9467-30459d28957f (old id 4223353)
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http://www.ncbi.nlm.nih.gov/pubmed/24361012?dopt=Abstract
date added to LUP
2014-01-05 22:52:44
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2017-09-24 03:10:16
@article{98e5f289-e270-4fe1-9467-30459d28957f,
  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.},
  author       = {Tattikota, Sudhir G and Rathjen, Thomas and McAnulty, Sarah J and Wessels, Hans-Hermann and Akerman, Ildem and van de Bunt, Martijn and Hausser, Jean and Esguerra, Jonathan and Musahl, Anne and Pandey, Amit K and You, Xintian and Chen, Wei and Herrera, Pedro L and Johnson, Paul R and O'Carroll, Donal and Eliasson, Lena and Zavolan, Mihaela and Gloyn, Anna L and Ferrer, Jorge and Shalom-Feuerstein, Ruby and Aberdam, Daniel and Poy, Matthew N},
  issn         = {1550-4131},
  language     = {eng},
  number       = {1},
  pages        = {122--134},
  publisher    = {Cell Press},
  series       = {Cell Metabolism},
  title        = {Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell.},
  url          = {http://dx.doi.org/10.1016/j.cmet.2013.11.015},
  volume       = {19},
  year         = {2014},
}