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

Background: 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.

Methods: 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.

Results: 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.

Conclusion: Resveratrol ameliorated glucose uptake and lipid metabolism of the GDM mice and adipocytes with IR by regulating miR-23a-3p/NOV axis.