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miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice

OBJECTIVE: 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....

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Autores principales: Dusaulcy, Rodolphe, Handgraaf, Sandra, Visentin, Florian, Vesin, Christian, Philippe, Jacques, Gosmain, Yvan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437597/
https://www.ncbi.nlm.nih.gov/pubmed/30711402
http://dx.doi.org/10.1016/j.molmet.2019.01.004
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author Dusaulcy, Rodolphe
Handgraaf, Sandra
Visentin, Florian
Vesin, Christian
Philippe, Jacques
Gosmain, Yvan
author_facet Dusaulcy, Rodolphe
Handgraaf, Sandra
Visentin, Florian
Vesin, Christian
Philippe, Jacques
Gosmain, Yvan
author_sort Dusaulcy, Rodolphe
collection PubMed
description OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-64375972019-04-11 miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice Dusaulcy, Rodolphe Handgraaf, Sandra Visentin, Florian Vesin, Christian Philippe, Jacques Gosmain, Yvan Mol Metab Original Article OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Elsevier 2019-01-18 /pmc/articles/PMC6437597/ /pubmed/30711402 http://dx.doi.org/10.1016/j.molmet.2019.01.004 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Dusaulcy, Rodolphe
Handgraaf, Sandra
Visentin, Florian
Vesin, Christian
Philippe, Jacques
Gosmain, Yvan
miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice
title miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice
title_full miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice
title_fullStr miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice
title_full_unstemmed miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice
title_short miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice
title_sort mir-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437597/
https://www.ncbi.nlm.nih.gov/pubmed/30711402
http://dx.doi.org/10.1016/j.molmet.2019.01.004
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