天麻素在L6肌管中促进葡萄糖消耗的作用和机制研究

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摘要目的研究天麻素（GSTD）在L6肌管中促进葡萄糖消耗的作用和可能机制。方法体外培养大鼠L6骨骼肌细胞并诱导分化成肌管，血清饥饿后以GSTD单独处理或与浓度为0.05 nmol/L的胰岛素联合处理24 h，以二甲双胍（Met）为阳性对照药。部分实验中L6肌管先以浓度为100 nmol/L的胰岛素处理24 h以诱导胰岛素抵抗，再进行药物处理。以试剂盒测定细胞糖消耗、L-乳酸释放和ATP产生，以Western blot和实时荧光定量反转录PCR检测目标蛋白和基因的表达水平。结果 GSTD浓度依赖性地促进L6肌管的基础糖消耗[与对照细胞比较，差异有统计学意义（P ＜ 0.05或P ＜ 0.01）]，并且显著增加胰岛素刺激的糖消耗[与单用胰岛素或GSTD处理的细胞比较，差异有统计学意义（P ＜ 0.05）]。在胰岛素抵抗状态下，浓度为500 μmol/L的GSTD仍能有效促进细胞糖消耗（P ＜ 0.05）。Met处理后显著增加细胞的L-乳酸释放并抑制ATP产生[与对照细胞比较，差异有高度统计学意义（P ＜ 0.01）]，但GSTD没有作用。GSTD显著上调L6肌管GLUT4蛋白和mRNA的表达，并且激活AMPK和Akt通路，表现为处理后p-AMPKα和p-Akt的水平显著增加[与对照细胞比较，差异有统计学意义（P ＜ 0.05或P ＜ 0.01）]。结论 GSTD作用于L6肌管显著增加其糖消耗并能克服胰岛素抵抗，其机制可能与GLUT4的上调以及AMPK和Akt通路的激活有关。

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	张勇孔维佳

关键词 ：天麻素, 葡萄糖消耗, 胰岛素抵抗, 糖酵解, 葡萄糖转运蛋白4, AMP依赖的蛋白激酶

Abstract：Objective To investigate the activities and possible mechanisms of gastrodin (GSTD) to promote glucose consumption in L6 myotubes. Methods Rat L6 skeletal muscle cells were cultured in vitro and differentiated into myotubes. After serum starvation, GSTD was used to treat the myotubes for 24 h, either alone or in combination with insulin at a concentration of 0.05 nmol/L. Metformin (Met) was used a positive control drug. In some experiments, L6 myotubes were treated with 100 nmol/L of insulin for 24 h to induce insulin resistance before drug treatment. Commercial kits were used to determine cell glucose consumption, L-lactate release, and ATP production. The expression levels of target proteins and genes were determined by Western blot and real-time quantitative reverse transcription-PCR (RT-PCR). Results GSTD promoted the basal glucose consumption of L6 myotubes in a concentration-dependent manner [comparing with control cells, the diferences were statistically significant (P ＜ 0.05 or P ＜ 0.01)]. In addition, GSTD greatly increased the insulin-stimulated glucose consumption [comparing with cells treated with insulin or GSTD alone, the diferences were statistically significant (P ＜ 0.05)]. In a state of insulin resistance, GSTD at a concentration of 500 μmol/L was still effective to promote cell glucose consumption (P ＜ 0.05). After treatment, Met significantly increased cellular L-lactate release but decreased ATP production [comparing with control cells, the diferences were highly statistically significant (P ＜ 0.01)]. However, GSTD did not have such effects. GSTD greatly up-regulated the protein and mRNA expression levels of GLUT4 in L6 myotubes. In addition, it activated the AMPK and Akt pathways, as indicated by the significant increase of p-AMPKα and p-Akt levels after treatment [comparing with control cells, the diferences were statistically significant (P ＜ 0.05 or P ＜ 0.01)]. Conclusion When used to treat L6 myotubes, GSTD greatly increases glucose consumption and is able to overcome insulin resistance. The mechanisms may be associated with the up-regulation of GLUT4 as well as the activation of AMPK and Akt pathways.

Key words： Gastrodin Glucose consumption Insulin resistance Glycolysis Glucose transporter 4 AMP-activated protein kinase

通讯作者: 孔维佳（1972.12-），男，博士，研究员；研究方向：分子医学与药物研究。

作者简介: 张勇（1987.9-），男，北京协和医学院2015级药理学专业在读博士研究生；研究方向：代谢性疾病药物药理学。

引用本文:

张勇孔维佳. 天麻素在L6肌管中促进葡萄糖消耗的作用和机制研究[J]. 中国医药导报, 2019, 16(4): 22-25.
ZHANG Yong KONG Weijia. Study of the effects and mechanisms of gastrodin to promote glucose consumption in L6 myotubes. 中国医药导报, 2019, 16(4): 22-25.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2019/V16/I4/22

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