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MicroRNA-7a regulates pancreatic β cell function

Latreille, Mathieu and Hausser, Jean and Stützer, Ina and Zhang, Quan and Hastoy, Benoit and Gargani, Sofia and Kerr-Conte, Julie and Pattou, Francois and Zavolan, Mihaela and Esguerra, Jonathan L. S. and Eliasson, Lena and Rülicke, Thomas and Rorsman, Patrik and Stoffel, Markus. (2014) MicroRNA-7a regulates pancreatic β cell function. Journal of Clinical Investigation, Vol. 124, H. 6. pp. 2722-2735.

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Official URL: http://edoc.unibas.ch/dok/A6263189

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Abstract

Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic β cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of β cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in β cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates β cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in β cells developed diabetes due to impaired insulin secretion and β cell dedifferentiation. Interestingly, perturbation of miR-7a expression in β cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine β cell mass. Furthermore, we found that miR-7a levels are decreased in obese/diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated β cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic β cells and support a role for miR-7 in the adaptation of pancreatic β cell function in obesity and type 2 diabetes.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Clinical Investigation
ISSN:0021-9738
e-ISSN:1558-8238
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Oct 2017 08:21
Deposited On:20 Jun 2014 07:56

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