Open AccessIdentification of a Panel of MiRNAs as Positive Regulators of Insulin Release in Pancreatic Β-Cells
Author(s) -
Hedong Lang,
YuTao Xiang,
Ning Lin,
Zhihua Ai,
Zhiqing You,
Jie Xiao,
Dan Liŭ,
Yating Yang
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000491717
Subject(s) - microrna , insulin , biology , taqman , pancreatic islets , glucose homeostasis , blot , luciferase , messenger rna , microbiology and biotechnology , downregulation and upregulation , real time polymerase chain reaction , endocrinology , islet , insulin resistance , gene , transfection , genetics
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 ELISA. 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 β-cells consisting of miRNAs, UCP2, and insulin and provide novel therapeutic targets for diabetes.