Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 48, Issue 1, Pages 185-193Publisher
KARGER
DOI: 10.1159/000491717
Keywords
Insulin release; Mitochondrial UCP2; MicroRNA; Beta cells
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Funding
- Youth Innovation Talent Fund [41732C11C]
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Background/Aims: MicroRNAs (miRNAs) are a novel class of small RNAs that participate in a variety of biological processes. Although miRNAs have been linked to insulin synthesis and glucose homeostasis, their role in the targeting of mitochondrial uncoupling protein 2 (UCP2), a negative modulator of insulin secretion, remains unclear. Methods: miRNA levels were determined by real-time quantitative PCR analysis using TaqMan probes, and insulin secretion from isolated islets was quantified by ELEA. Effects of miRNAs on UCP2 expression were checked with a luciferase assay and western blotting analysis. Results: An overall change in a set of miRNAs was discovered, with miR-15a, miR-424, miR-497, and miR-185 coinciding with insulin levels in islets maintained under high-glucose conditions. Moreover, experiments in MIN6 cells illustrated that miR-15a, miR-424, miR-497, and miR-185 positively regulated insulin biosynthesis by co-inhibiting UCP2 expression. Furthermore, the four miRNAs were found to post-transcriptionally repress UCP2 expression by directly targeting the 3'UTR of UCP2 mRNA. Conclusions: Thus, our results shed further light on the regulatory network in p-cells consisting of miRNAs, UCP2, and insulin and provide novel therapeutic targets for diabetes. (C) 2018 The Author(s) Published by S Karger AG, Basel
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