Resveratrol ameliorates the glucose uptake and lipid metabolism in gestational diabetes mellitus mice and insulin-resistant adipocytes via miR-23a-3p/NOV axis

•Resveratrol relieved the symptoms of GDM mice.•Resveratrol enhanced the glucose intake in insulin-resistance cells.•Resveratrol increased miR-23a-3p expression and decreased NOV expression.•MiR-23a-3p targeted NOV.•Role of Resveratrol in GDM was mediated by the miR-23a-3p/NOV axis. Resveratrol impr...

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Veröffentlicht in:Molecular immunology 2021-09, Vol.137, p.163-173
Hauptverfasser: Zheng, Tao, Chen, Hainan
Format: Artikel
Sprache:eng
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Zusammenfassung:•Resveratrol relieved the symptoms of GDM mice.•Resveratrol enhanced the glucose intake in insulin-resistance cells.•Resveratrol increased miR-23a-3p expression and decreased NOV expression.•MiR-23a-3p targeted NOV.•Role of Resveratrol in GDM was mediated by the miR-23a-3p/NOV axis. Resveratrol improves insulin-resistance (IR) of gestational diabetes mellitus (GDM) mice. Low-expressed miR-23a-3p in diabetes patients regulates IR of adipocytes. Hence, we speculated the effect of Res on GDM mice was realized through regulating miR-23a-3p. The GDM model was established in mice by high-fat diet, treated with miR-23a-3p antagomiR, and further performed with glucose and insulin tolerance tests. The bodyweight, serum glucose and serum insulin, and the expressions of miR-23a-3p and nephroblastoma overexpressed (NOV) in mouse adipose tissues were detected. MiR-23a-3p target was identified by Starbase and dual-luciferase reporter. Then, an IR adipocyte model was established by dexamethasone-inducing and further treated with Resveratrol or transfected with miR-23a-3p inhibitor or siNOV. The cell glucose intake was detected by radioimmunoassay. The expressions of miR-23a-3p, NOV, Adiponectin, Leptin, p-PI3K, PI3K, p-Akt, and Akt in the adipocytes were determined by qPCR or Western blot. Resveratrol decreased bodyweight, glucose level, insulin level, and the expressions of miR-23a-3p and NOV in the GDM mice, which was reversed by miR-23a-3p antagomiR. MiR-23a-3p targeted NOV. Resveratrol increased the glucose intake and the expressions of miR-23a-3p, Adiponectin, Leptin, p-PI3K, and p-Akt, decreased NOV expression in the IR adipocytes. The effect of the miR-23a-3p inhibitor on adipocytes with IR was opposite to Resveratrol, and the effects siNOV was the same as Resveratrol, except for its effect on miR-23a-3p expression. Effect of Res on the adipocytes with IR was counteracted by miR-23a-3p inhibitor whose effect was reversed by siNOV. Resveratrol ameliorated glucose uptake and lipid metabolism of the GDM mice and adipocytes with IR by regulating miR-23a-3p/NOV axis.
ISSN:0161-5890
1872-9142
DOI:10.1016/j.molimm.2021.06.011