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.

中文翻译：

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白藜芦醇通过 miR-23a-3p/NOV 轴改善妊娠糖尿病小鼠和胰岛素抵抗脂肪细胞的葡萄糖摄取和脂质代谢

背景

白藜芦醇可改善妊娠糖尿病 (GDM) 小鼠的胰岛素抵抗 (IR)。糖尿病患者中低表达的 miR-23a-3p 调节脂肪细胞的 IR。因此，我们推测 Res 对 GDM 小鼠的影响是通过调节 miR-23a-3p 实现的。

方法

小鼠通过高脂饮食建立GDM模型，用miR-23a-3p antagomiR处理，并进一步进行葡萄糖和胰岛素耐量试验。检测小鼠脂肪组织中的体重、血清葡萄糖和血清胰岛素，以及miR-23a-3p和肾母细胞瘤过表达（NOV）的表达。MiR-23a-3p 目标由 Starbase 和双荧光素酶报告基因确定。然后，通过地塞米松诱导建立IR脂肪细胞模型，并进一步用白藜芦醇处理或转染miR-23a-3p抑制剂或siNOV。通过放射免疫测定法检测细胞葡萄糖摄入量。通过qPCR或Western印迹测定脂肪细胞中miR-23a-3p、NOV、脂联素、瘦素、p-PI3K、PI3K、p-Akt和Akt的表达。

结果

白藜芦醇降低 GDM 小鼠的体重、葡萄糖水平、胰岛素水平以及 miR-23a-3p 和 NOV 的表达，而这被 miR-23a-3p antagomiR 逆转。MiR-23a-3p 以 11 月为目标。白藜芦醇增加葡萄糖摄入量和 miR-23a-3p、脂联素、瘦素、p-PI3K 和 p-Akt 的表达，降低 IR 脂肪细胞中 NOV 的表达。miR-23a-3p抑制剂对IR脂肪细胞的作用与白藜芦醇相反，siNOV的作用与白藜芦醇相同，只是对miR-23a-3p表达的影响不同。Res对具有IR的脂肪细胞的影响被miR-23a-3p抑制剂抵消，其作用被siNOV逆转。

结论

白藜芦醇通过调节 miR-23a-3p/NOV 轴改善 GDM 小鼠和脂肪细胞的葡萄糖摄取和脂质代谢。