糖耐康对肥胖Zucker大鼠血糖的影响及其机制

目的：观察中药复方糖耐康对肥胖Zucker大鼠糖代谢和胰岛素抵抗的影响。 方法：6周龄雄性肥胖Zucker大鼠12只，适应性喂养2周后，随机分为对照组和糖耐康组（3.24 g/kg），所有大鼠给予高脂饲料喂养，疗程为4周。每周检测体质量和血糖；入组前和治疗14、28 d时行口服葡萄糖耐量实验（oral glucose tolerance test，OGTT）并检测空腹血清胰岛素水平；第28天时检测空腹血脂4项和血浆游离脂肪酸（free fatty acids，FFA）水平；第29天时进行高胰岛素正葡萄糖钳夹实验检测平均葡萄糖输注率（glucose infusion rate，GIR）；实验结束后处死大鼠并取材，检测骨骼肌中蛋白激酶B（protein kinase B，PKB/Akt）、磷酸化蛋白激酶B（phospho-Akt, p-Akt/Thr308）、葡萄糖转运蛋白4（glucose transporter protein 4，GLUT4）的表达和脂肪组织GLUT4的蛋白表达。 结果：与对照组相比，治疗4周后，糖耐康组血清胰岛素水平没有变化，餐后血糖和OGTT中120 min时的血糖水平均显著下降；糖耐康组高胰岛素正葡萄糖钳夹实验后GIR显著提高；糖耐康能显著增加骨骼肌Akt、p-Akt（Thr308）的蛋白表达，减少脂肪组织GLUT4的蛋白表达；糖耐康有降低体质量、血脂（三酰甘油、胆固醇、低密度脂蛋白）和FFA含量的趋势，但两组比较差异无统计学意义。 结论：糖耐康可能是通过增加骨骼肌Akt和p-Akt（Thr308）的表达，增强GLUT4的葡萄糖转运能力来实现降低血糖，改善外周胰岛素抵抗的功效。

Antidiabetic effects of Tangnaikang on obese Zucker rats and the mechanism

Objective: To observe the effects of Tangnaikang (TNK), a compound traditional Chinese herbal medicine, on glucose metabolism and insulin resistance in obese Zucker rats. Methods: Twelve male obese Zucker rats, 6 weeks old, were randomly divided into control group and TNK group (3.24 g/kg) after being fed for 2 weeks. All rats received high-fat diet and 4-week treatment. Body weight and blood glucose were tested every week. Oral glucose tolerance test (OGTT) was performed and fasting insulin level was tested on days 0, 14 and 28. Triglyceride, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acids (FFA) were tested on day 28. Glucose infusion rate (GIR) was tested by hyperinsulinemic-euglycemic clamp from day 29. The protein expressions of protein kinase B (Akt), phospho-Akt (p-Akt) (Thr308) and glucose transporter protein 4 (GLUT4) in skeletal muscle and GLUT4 in adipose tissue were measured after hyperinsulinemic-euglycemic clamp test.Results: Compared with the control group, the fed blood glucose level and glucose level of OGTT at 120 min had a significant decline in TNK group on day 28, and TNK caused no alteration of the fasting serum insulin, and the GIR increased significantly in hyperinsulinemic-euglycemic clamp study. Furthermore, TNK increased Akt and p-Akt (Thr308) protein expressions in skeletal muscle and decreased the protein expression of GLUT4 in white adipose tissue. Body weight, and triglyceride, cholesterol, LDL-C and FFA contents were slightly decreased in the TNK group, but there were no statistically significant effects.Conclusion: TNK increases the protein expressions of Akt and p-Akt (Thr308) of the signal transduction pathway to influence the translocation of GLUT4 in skeletal muscle and improves glucose metabolism by reducing insulin resistance.