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miR-184 regulates pancreatic β-cell function according to glucose metabolism

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Item Type:Article
Title:miR-184 regulates pancreatic β-cell function according to glucose metabolism
Creators Name:Tattikota, S.G., Rathjen, T., Hausser, J., Khedkar, A., Kabra, U.D., Pandey, V.K., Sury, M.D., Wessels, H.H., Mollet, I.G., Eliasson, L., Selbach, M., Zinzen, R.P., Zavolan, M., Kadener, S., Tschöp, M., Jastroch, M., Friedländer, M.R. and Poy, M.N.
Abstract:In response to fasting or hyperglycemia, the pancreatic {beta}-cell alters its output of secreted insulin; however the pathways governing this adaptive response are not entirely established. While 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 {beta}-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 {beta}-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon administration of a sucrose-rich diet in Drosophila demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 (Ago2) remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Ago2 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.
Keywords:Glucose Metabolism, microRNA (miRNA), beta-Cell, Argonaute, Pancreatic Islet, Insulin, Insulin Secretion, microRNA Mechanism, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology
Volume:290
Number:33
Page Range:20284-20294
Date:14 August 2015
Official Publication:https://doi.org/10.1074/jbc.M115.658625
PubMed:View item in PubMed

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