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MiR-184 expression is regulated by AMPK in pancreatic islets.

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Title: MiR-184 expression is regulated by AMPK in pancreatic islets.
Authors: Martinez-Sanchez, A
Nguyen-Tu, M-S
Cebola, I
Yavari, A
Marchetti, P
Piemonti, L
De Koning, E
Shapiro, AMJ
Johnson, P
Sakamoto, K
Smith, DM
Leclerc, I
Ashrafian, H
Ferrer, J
Rutter, GA
Item Type: Journal Article
Abstract: AMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β-cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits (βAMPKdKO mice) impairs insulin secretion in vivo and β-cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β-cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β-cells. We identified 14 down-regulated and 9 up-regulated miRNAs in βAMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichment in pathways important for β-cell function and identity. The most down-regulated miRNA was miR-184 (miR-184-3p), an important regulator of β-cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR-184 expression. Additionally, we reveal sexual dimorphism in miR-184 expression in mouse and human islets. Collectively, these data demonstrate that glucose-mediated changes in AMPK activity are central for the regulation of miR-184 and other miRNAs in islets and provide a link between energy status and gene expression in β-cells.-Martinez-Sanchez, A., Nguyen-Tu, M.-S., Cebola, I., Yavari, A., Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K., Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., Rutter, G. A. MiR-184 expression is regulated by AMPK in pancreatic islets.
Issue Date: 1-May-2018
Date of Acceptance: 11-Dec-2017
URI: http://hdl.handle.net/10044/1/63379
DOI: https://dx.doi.org/10.1096/fj.201701100R
ISSN: 0892-6638
Publisher: Federation of American Society of Experimental Biology
Start Page: 2587
End Page: 2600
Journal / Book Title: FASEB Journal
Volume: 32
Issue: 5
Copyright Statement: © The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons. org/licenses/by/4.0/) which permits u nrestricted use, distribution, and re- production in any medium, provided the original work is properly cited.
Sponsor/Funder: Medical Research Council (MRC)
Wellcome Trust
Medical Research Council (MRC)
Funder's Grant Number: MR/K001981/1
101033/C/13/Z
MR/P023223/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Cell Biology
Life Sciences & Biomedicine - Other Topics
miRNAs
glucose
beta cell
diabetes
STIMULATED INSULIN-SECRETION
BETA-CELL FUNCTION
GLUCOSE-METABOLISM
PROTEIN-KINASE
MICRORNAS
CANCER
MICE
IDENTITY
MIRNAS
MODELS
β cell
β-cell
0601 Biochemistry And Cell Biology
0606 Physiology
1116 Medical Physiology
Publication Status: Published
Open Access location: http://10.0.4.72/fj.201701100R
Online Publication Date: 2018-04-26
Appears in Collections:Department of Medicine



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