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miR-184 Regulates Pancreatic β-Cell Function According to Glucose Metabolism

Tattikota, Sudhir G. and Rathjen, Thomas and Hausser, Jean and Khedkar, Aditya and Kabra, Uma D. and Pandey, Varun and Sury, Matthias and Wessels, Hans-Hermann and Mollet, Inês G. and Eliasson, Lena and Selbach, Matthias and Zinzen, Robert P. and Zavolan, Mihaela and Kadener, Sebastian and Tschöp, Matthias H. and Jastroch, Martin and Friedländer, Marc R. and Poy, Matthew N.. (2015) miR-184 Regulates Pancreatic β-Cell Function According to Glucose Metabolism. Journal of biological chemistry, Vol. 290, H. 33. pp. 20284-20294.

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Official URL: http://edoc.unibas.ch/dok/A6428730

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Abstract

In response to fasting or hyperglycemia, the pancreatic β-cell alters its output of secreted insulin; however, the pathways governing this adaptive response are not entirely established. Although the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the β-cell, regulates compensatory proliferation and secretion during insulin resistance. Consistent with previous studies showing miR-184 suppresses insulin release, expression of this miRNA was increased in islets after fasting, demonstrating an active role in the β-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon the administration of a sucrose-rich diet in Drosophila, demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Argonaute2 in the presence of miR-184 rescued suppression of miR-375-targeted genes, suggesting these genes act in a coordinated manner during changes in the metabolic context. Together, these results highlight the adaptive role of miR-184 according to glucose metabolism and suggest the regulatory role of this miRNA in energy homeostasis is highly conserved.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela and Hausser, Jean
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society of Biological Chemists
ISSN:0021-9258
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:02 Oct 2015 10:01
Deposited On:02 Oct 2015 10:01

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