Journal article
miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice.
- Dusaulcy R Laboratory of Molecular Diabetes, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland. Electronic address: rodolphe.dusaulcy@unige.ch.
- Handgraaf S Laboratory of Molecular Diabetes, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland.
- Visentin F Laboratory of Molecular Diabetes, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland.
- Vesin C Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, Geneva, Switzerland.
- Philippe J Laboratory of Molecular Diabetes, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland.
- Gosmain Y Laboratory of Molecular Diabetes, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland.
- 2019-02-04
Published in:
- Molecular metabolism. - 2019
Alpha-cell
Apoptosis
Glucagon
Proliferation
Type 2 diabetes
miR-132-3p
Animals
Cells, Cultured
Down-Regulation
Glucagon-Secreting Cells
Humans
Mice
Mice, Obese
MicroRNAs
Obesity
English
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.
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1016/j.molmet.2019.01.004
- PMID 30711402
- Persistent URL
- https://sonar.ch/global/documents/46659
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