Argonaute2 mediates compensatory expansion of the pancreatic beta cell
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Published version
Author(s)
Type
Journal Article
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.
Date Issued
2014-01-07
Date Acceptance
2013-11-10
ISSN
1932-7420
Publisher
Elsevier (Cell Press)
Start Page
122
End Page
134
Journal / Book Title
Cell Metabolism
Volume
19
Issue
1
Copyright Statement
Open access under CC BY license.
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Endocrinology & Metabolism
CELL BIOLOGY
ENDOCRINOLOGY & METABOLISM
INSULIN-SECRETION
GENE-EXPRESSION
MESSENGER-RNAS
MICRORNAS
STRESS
REVEALS
MICE
MASS
HOMEOSTASIS
METABOLISM
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Endocrinology & Metabolism
MESSENGER-RNAS
INSULIN
MICRORNAS
REVEALS
MICE
METABOLISM
MECHANISMS
CROSSTALK
TARGETS
ROLES
Animals
Argonaute Proteins
Cell Proliferation
Diet, Ketogenic
Gene Expression Regulation
Gene Silencing
Humans
Insulin Resistance
Insulin-Secreting Cells
Mice
Mice, Obese
MicroRNAs
Animals
Humans
Mice
Mice, Obese
Insulin Resistance
MicroRNAs
Cell Proliferation
Gene Expression Regulation
Gene Silencing
Insulin-Secreting Cells
Argonaute Proteins
Diet, Ketogenic
0601 Biochemistry and Cell Biology
1101 Medical Biochemistry and Metabolomics
Endocrinology & Metabolism
Publication Status
Published
OA Location
http://www.sciencedirect.com/science/article/pii/S1550413113004646