银杏叶提取物对胰岛素抵抗大鼠骨骼肌 GLUT4 表达的影响

 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。 Western Blot 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 GLUT4 mRNA 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 GLUT4 mRNA 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。

Effects of Ginkgo Biloba Extract on GLUT4 Expression in Skeletal Muscle of Insulin Resistant Rats

OBJECTIVE To study the influence of ginkgo biloba extract （ EGB ） on the GLUT4 expression in insulin resistant rat skeletal muscle and investigate the molecular mechanism of its insulin sensitization. METHODS The insulin resistant rat model was duplicated by high-fat diets, and then the model rats were intervened by different dosage EGB or rosiglitazone for four weeks. The serum total cho lesterol(TC), triglyeride(TG), fasting blood glucose(FBG), and fasting insulin(FINS) were measured after the intervention. The hyperinsulinaemic-euglycaemic clamp was performed to evaluate the insulin sensitization of EGB. The skeletal muscle GLUT4 protein level was assayed by western blot. The expression of GLUT4 mRNA was detected by real time RT-PCR. RESULTS The insulin resistant rat model was successfully duplicated by high-fat diet, in which the glucose infusion rate (GIR) decreased significantly, the serum FBG, FINS, TC and TG increased remarkably, and t he GLUT4 protein level and GLUT4 mRNA expression in skeletal muscle decreased significantly compared with the normal control group ( P < 0.05 or P < 0.01). EGB intervention increased the GIR, reduced the concentration of serum TC, TG, TBG and FINS, up-regulated the GLUT4 expression of skeletal muscle. The middle and high dosage EGB intervention improved these parameters more effectively than low dosage. CONCLUSION EGB can improve the insulin resistance induced by high-fat diets. The up-regulation of GLUT4 expression in skeletal muscle is associated with its insulin sensitization.