miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice.
Alpha-cell
Apoptosis
Glucagon
Proliferation
Type 2 diabetes
miR-132-3p
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
22
08
2018
revised:
11
01
2019
accepted:
12
01
2019
pubmed:
4
2
2019
medline:
14
4
2020
entrez:
4
2
2019
Statut:
ppublish
Résumé
Diabetes is a complex disease implicating several organs and cell types. Within the islets, dysregulation occurs in both alpha- and beta-cells, leading to defects of insulin secretion and increased glucagon secretion. Dysregulation of alpha-cells is associated with transcriptome changes. We hypothesized that microRNAs (miRNAs) which are negative regulators of mRNA stability and translation could be involved in alpha-cell alterations or adaptations during type 2 diabetes. miRNA microarray analyses were performed on pure alpha- and beta-cells from high-fat diet fed obese hyperglycemic mice and low-fat diet fed controls. Then, the most regulated miRNA was overexpressed or inhibited in primary culture of mouse and human alpha-cells to determine its molecular and functional impact. 16 miRNAs were significantly regulated in alpha-cells of obese hyperglycemic mice and 28 in beta-cells. miR-132-3p had the strongest regulation level in alpha-cells, where it was downregulated, while we observed an opposite upregulation in beta-cells. In vitro experiments showed that miR-132-3p, which is inversely regulated by somatostatin and cAMP, is a positive modulator of alpha-cell proliferation and implicated in their resistance to apoptosis. These effects are associated with the regulation of a series of genes, including proliferation and stress markers Mki67 and Bbc3 in mouse and human alpha-cells, potentially involved in miR-132-3p functions. Downregulation of miR-132-3p in alpha-cells of obese diabetic mice may constitute a compensatory mechanism contributing to keep glucagon-producing cell number constant in diabetes.
Identifiants
pubmed: 30711402
pii: S2212-8778(18)30841-X
doi: 10.1016/j.molmet.2019.01.004
pmc: PMC6437597
pii:
doi:
Substances chimiques
MIRN132 microRNA, human
0
MIRN132 microRNA, mouse
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
84-95Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.
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