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目的观察银杏叶提取物对高脂饮食所诱导的胰岛素抵抗大鼠骨骼肌葡萄糖转运蛋白4(GLUT4)表达的影响,探讨银杏叶提取物改善胰岛素敏感性的分子机制。方法采用高脂喂养的方法建立胰岛素抵抗大鼠模型,并给予为期4周的不同剂量银杏叶提取物腹腔注射干预,以罗格列酮作为阳性对照。干预后测定大鼠血清总胆固醇、甘油三酯、空腹血糖、空腹胰岛素等指标,高胰岛素-正常葡萄糖钳夹实验评价银杏叶提取物的胰岛素增敏作用。WesternBlot测定大鼠骨骼肌GLUT4蛋白水平,实时荧光定量RT-PCR测定大鼠骨骼肌GLUT4mRNA表达。结果高脂饮食成功建立胰岛素抵抗大鼠模型,与正常对照组相比,葡萄糖输注率显著下降,空腹血糖、空腹胰岛素、总胆固醇、甘油三酯升高(P<0.01),骨骼肌GLUT4蛋白水平下降(P<0.05),骨骼肌GLUT4mRNA下降(P<0.01)。银杏叶提取物干预使葡萄糖输注率增加,并不同程度地降低总胆固醇、甘油三酯、空腹血糖、空腹胰岛素,同时骨骼肌GLUT4表达上调,中、高剂量银杏叶提取物对上述指标的改善更加明显,优于低剂量组。结论银杏叶提取物能够改善高脂饮食诱导的胰岛素抵抗状态,其胰岛素增敏机制与增加骨骼肌GLUT4的表达有关。
Objective To observe the effect of Ginkgo biloba extract on the expression of skeletal muscle glucose transporter 4 (GLUT4) in insulin-resistant rats induced by high-fat diet, and to explore the molecular mechanism of Ginkgo biloba extract in improving insulin sensitivity. Methods The rat model of insulin resistance was established by high-fat feeding. Four weeks’ different doses of Ginkgo biloba extract were injected intraperitoneally. Rosiglitazone was used as a positive control. After intervention, serum total cholesterol, triglyceride, fasting blood glucose, fasting insulin and other indicators were measured. High insulin-normal glucose clamp experiment was used to evaluate insulin sensitization of Ginkgo biloba extract. The protein level of GLUT4 in skeletal muscle of rats was determined by Western Blot, and the expression of GLUT4 mRNA in skeletal muscle of rats was measured by real-time fluorescence quantitative RT-PCR. Results The rat model of insulin resistance was successfully established on a high-fat diet. Compared with the normal control group, the glucose infusion rate was significantly decreased, and the fasting blood glucose, fasting insulin, total cholesterol, and triglyceride were elevated (P<0.01). The skeletal muscle GLUT4 protein The level decreased (P<0.05), and GLUT4 mRNA in skeletal muscle decreased (P<0.01). Ginkgo biloba extract intervention increased the rate of glucose infusion, and decreased total cholesterol, triglyceride, fasting blood glucose, and fasting insulin to varying degrees. Meanwhile, the expression of GLUT4 in skeletal muscles was up-regulated. The improvement of the above indexes was improved by middle and high dose Ginkgo biloba extracts. More obvious, better than low-dose group. Conclusion Ginkgo biloba extract can improve insulin resistance induced by high-fat diet, and its mechanism of insulin sensitization is related to the increase of GLUT4 expression in skeletal muscle.