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Keywords:

  • diabetic myopathy;
  • glycogen synthase kinase 3;
  • oxidative stress;
  • resveratrol;
  • type 1 diabetes
  • 糖尿病肌病,糖原合成酶激酶3,氧化应激,白藜芦醇,1型糖尿病

Abstract

Background

This study aimed to investigate the differential protective effect of resveratrol (RSV) on oxidative stress and metabolic signaling pathways in fast- and slow-twitch skeletal muscles of rats with diabetes.

Methods

Diabetic rats were induced by streptozotocin (STZ) for 2 weeks and then administered with RSV (1, 10 and 100 μg/kg per day) for 1 week. We determined oxidative stress and protein expression by lucigenin-mediated chemiluminescence and Western immunoblot.

Results

The superoxide anion production and copper-zinc superoxide dismutase (CuZnSOD) protein level were increased in fast-twitch muscle than in slow-twitch muscle of diabetes. The Akt and glycogen synthase kinase 3 (GSK-3) phosphorylations were reduced in both fast- and slow-twitch muscles of diabetes. Oxidative stress and GSK-3 dephosphorylation were corrected by RSV treatment in both fast- and slow-twitch muscles of diabetes. Furthermore, RSV treatment downregulated CuZnSOD protein level in diabetic fast-twitch muscle. In diabetic slow-twitch muscle, RSV treatment elevated manganese SOD (MnSOD) and phosphorylated Akt protein levels and reduced acetyl-CoA carboxylase (ACC) phosphorylation.

Conclusions

Our results suggested that fast-twitch muscle incurred more oxidative stress, whereas slow-twitch muscle altered metabolic signaling molecules activities under diabetic status. The antidiabetic effect of RSV on fast- and slow-twitch skeletal muscles was mediated by different antioxidative and metabolic signals.

摘要

背景

该研究的目的是调查白藜芦醇(Resveratrol,RSV)对糖尿病大鼠的快反应与慢反应骨骼肌的氧化应激与代谢信号通路是否具有不同的保护效应。

方法

使用链脲霉素2周后诱导出糖尿病大鼠,接着使用RSV(每日1、10与100 μg/kg)治疗1周。使用光泽精介导的化学发光法以及西方免疫印迹法来测定氧化应激与蛋白表达。

结果

与在糖尿病大鼠的慢反应肌肉中观察到的相比,快反应肌肉中的超氧负离子生成以及铜-锌超氧化物歧化酶(CuZnSOD)的蛋白含量有所增加。在糖尿病大鼠的快反应与慢反应肌肉中,Akt与糖原合成酶激酶3(GSK-3)磷酸化都有所减少。在糖尿病大鼠的快反应与慢反应肌肉中,氧化应激与GSK-3脱磷酸作用都可以被RSV治疗所矫正。此外,在糖尿病大鼠的快反应肌肉中,RSV治疗可使CuZnSOD的蛋白含量向下调节。在糖尿病大鼠的慢反应肌肉中,RSV治疗可使锰SOD与磷酸化Akt的蛋白含量增加,并且使乙酰辅酶A羧化酶磷酸化减少。

结论

我们的研究结果提示,在糖尿病状态下,快反应肌肉承担的氧化应激更多,然而慢反应肌肉可以改变代谢信号分子的活性。RSV在快反应与慢反应骨骼肌中的抗糖尿病效应是通过不同的抗氧化与代谢信号来介导的。