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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4223353
- author
- 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. (More)
- Tattikota, Sudhir G
; Rathjen, Thomas
; McAnulty, Sarah J
; Wessels, Hans-Hermann
; Akerman, Ildem
; van de Bunt, Martijn
; Hausser, Jean
; Esguerra, Jonathan
LU
; Musahl, Anne
; Pandey, Amit K
; You, Xintian
; Chen, Wei
; Herrera, Pedro L
; Johnson, Paul R
; O'Carroll, Donal
; Eliasson, Lena
LU
; Zavolan, Mihaela
; Gloyn, Anna L
; Ferrer, Jorge
; Shalom-Feuerstein, Ruby
; Aberdam, Daniel
and Poy, Matthew N
(Less)
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Metabolism
- volume
- 19
- issue
- 1
- pages
- 122 - 134
- publisher
- Cell Press
- external identifiers
-
- wos:000329431200014
- pmid:24361012
- scopus:84891867862
- pmid:24361012
- ISSN
- 1550-4131
- DOI
- 10.1016/j.cmet.2013.11.015
- language
- English
- LU publication?
- yes
- id
- 98e5f289-e270-4fe1-9467-30459d28957f (old id 4223353)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24361012?dopt=Abstract
- date added to LUP
- 2016-04-01 10:18:29
- date last changed
- 2022-04-20 00:47:48
@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 = {{https://lup.lub.lu.se/search/files/1732871/4437323}},
doi = {{10.1016/j.cmet.2013.11.015}},
volume = {{19}},
year = {{2014}},
}