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Title: Argonaute2 mediates compensatory expansion of the pancreatic ß-cell      
dateReleased:
02-06-2014
description:
Pancreatic ß-cells adapt to compensate for the increased metabolic demand during insulin resistance. While the microRNA pathway has an essential role in the expansion of ß-cell mass, the extent of its contribution is unclear. Here we show that miR-184 is silenced in the pancreatic islets of several insulin-resistant mouse models and in the islets of 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. While over-expression of Ago2 increased ß-cell proliferation, conditional deletion decreased ß-cell number. Moreover, restored expression of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory ß-cell expansion. Loss of Ago2 expression during insulin resistance blocked ß-cell growth and relieved the regulation of miR-375-targeted genes including the growth suppressor Cadm1. This study identifies the regulation of Ago2 by miR-184 as an essential component of the compensatory response to promote proliferation during insulin resistance. MIN6 cells were transfected with Doxycyline responsive plasmids including the tetO-184 construct in biological triplicates for every time point. The conditions included untransfected control (CTR, induced), Transfected Control (TC, uninduced) along the time points of miR-184 overexpression in 16, 24, 48, and 72 hours of doxycycline treatment.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-46623
refinement:
raw
alternateIdentifiers:
46623
keywords:
functional genomics
dateModified:
06-03-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-MEXP-1175
name:
Illumina MouseWG-6 v2.0 Expression BeadChip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-46623/E-GEOD-46623.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-46623/E-GEOD-46623.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46623
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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