Khamaisi M, Potashnik R, Tirosh A, Demshchak E, Rudich A, Tritschler H, Wessel K, Bashan N
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Metabolism. 1997 Jul;46(7):763-8. doi: 10.1016/s0026-0495(97)90120-7.
Alpha lipoic acid (lipoate [LA]), a cofactor of alpha-ketodehydrogenase, exhibits unique antioxidant properties. Recent studies suggest a direct effect of LA on glucose metabolism in both human and experimental diabetes. This study examines the possibility that LA positively affects glucose homeostasis in streptozotocin (STZ)-induced diabetic rats by altering skeletal muscle glucose utilization. Blood glucose concentration in STZ-diabetic rats following 10 days of intraperitoneal (i.p.) injection of LA 30 mg/kg was reduced compared with that in vehicle-treated diabetic rats (495 +/- 131 v 641 +/- 125 mg/dL in fed state, P = .003, and 189 +/- 48 v 341 +/- 36 mg/dL after 12-hour fast, P = .001). No effect of LA on plasma insulin was observed. Gastrocnemius muscle crude membrane GLUT4 protein was elevated both in control and in diabetic rats treated with LA by 1.5- and 2.8-fold, respectively, without significant changes in GLUT4 mRNA levels. Gastrocnemius lactic acid was increased in diabetic rats (19.9 +/- 5.5 v 10.4 +/- 2.8 mumol/g muscle, P < .05 v nondiabetic rats), and was normal in LA-treated diabetic rats (9.1 +/- 5.0 mumol/g muscle). Insulin-stimulated 2-deoxyglucose (2 DG) uptake into isolated soleus muscle was reduced in diabetic rats compared with the control group (474 +/- 15 v 568 +/- 52 pmol/mg muscle 30 min, respectively, P = .05). LA treatment prevented this reduction, resulting in insulin-stimulated glucose uptake comparable to that of nondiabetic animals. These results suggest that daily LA treatment may reduce blood glucose concentrations in STZ-diabetic rats by enhancing muscle GLUT4 protein content and by increasing muscle glucose utilization.
α-硫辛酸（硫辛酸盐[LA]）作为α-酮脱氢酶的一种辅因子，具有独特的抗氧化特性。最近的研究表明，LA对人类和实验性糖尿病的葡萄糖代谢有直接影响。本研究探讨了LA通过改变骨骼肌葡萄糖利用，对链脲佐菌素（STZ）诱导的糖尿病大鼠的葡萄糖稳态产生积极影响的可能性。与溶剂处理的糖尿病大鼠相比，腹腔注射（i.p.）30 mg/kg LA 10天后，STZ糖尿病大鼠的血糖浓度降低（进食状态下分别为495±131和641±125 mg/dL，P = 0.003；禁食12小时后分别为189±48和341±36 mg/dL，P = 0.001）。未观察到LA对血浆胰岛素有影响。对照组和接受LA治疗的糖尿病大鼠腓肠肌粗膜GLUT4蛋白分别升高了1.5倍和2.8倍，而GLUT4 mRNA水平无显著变化。糖尿病大鼠腓肠肌乳酸增加（19.9±5.5对非糖尿病大鼠的10.4±2.8 μmol/g肌肉，P < 0.05），接受LA治疗的糖尿病大鼠则正常（9.1±5.0 μmol/g肌肉）。与对照组相比，糖尿病大鼠分离的比目鱼肌中胰岛素刺激的2-脱氧葡萄糖（2-DG）摄取减少（分别为474±15和568±52 pmol/mg肌肉30分钟，P = 0.05）。LA治疗可防止这种减少，使胰岛素刺激的葡萄糖摄取与非糖尿病动物相当。这些结果表明，每日LA治疗可能通过增加肌肉GLUT4蛋白含量和提高肌肉葡萄糖利用率来降低STZ糖尿病大鼠的血糖浓度。
