Khamaisi M, Rudich A, Beeri I, Pessler D, Friger M, Gavrilov V, Tritschler H, Bashan N
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Antioxid Redox Signal. 1999 Winter;1(4):523-35. doi: 10.1089/ars.1999.1.4-523.
Data suggesting the involvement of increased oxidative stress in the pathophysiology of diabetes has raised interest in the potential therapeutic benefit of antioxidants. Although beneficial metabolic effects of antioxidant supplementation have been suggested, an antioxidant mode of action, particularly in skeletal muscle, has not been documented. In the present study, we evaluate the metabolic effects of a gamma-linolenic acid-alpha-lipoic acid conjugate (GLA-LA) in streptozotocin-induced diabetic rats, and assess its potential mode of action by comparing its effects with equimolar administration of LA and GLA alone. Ten days of oral supplementation of 20 mg/kg body weight GLA-LA, but not LA or GLA alone, caused a mild reduction in fasting blood glucose concentration as compared with vehicle-treated diabetic rats (375 +/- 11 vs. 416 +/- 16 mg/dl, p = 0.03), with no change in fasting plasma insulin levels. A peripheral insulin-sensitizing effect could be observed with GLA-LA, LA, and GLA treatments, as demonstrated by a significant (p < 0.04) 23%, 13%, and 10% reduction, respectively, in the area under the glucose curve following an intravenous insulin tolerance test. This effect was associated with a 67% and 50% increase in GLUT4 protein content in the membranes of gastrocnemius muscle of GLA-LA and LA-treated animals, respectively; however, no change was observed with GLA treatment alone. Interestingly, both GLA-LA and LA treatments corrected a diabetes-related decrease in the gastrocnemius muscle low-molecular-weight reduced thiols content. These data demonstrate insulin-sensitizing properties of the GLA-LA conjugate by distinct mechanisms attributable to each of its components, which are associated with antioxidant effects.
有数据表明氧化应激增加参与了糖尿病的病理生理过程，这引发了人们对抗氧化剂潜在治疗益处的兴趣。尽管已表明补充抗氧化剂具有有益的代谢作用，但其作用方式，尤其是在骨骼肌中的作用方式，尚未得到证实。在本研究中，我们评估了γ-亚麻酸-α-硫辛酸共轭物（GLA-LA）对链脲佐菌素诱导的糖尿病大鼠的代谢影响，并通过将其与等摩尔单独给予硫辛酸（LA）和γ-亚麻酸（GLA）的效果进行比较，评估其潜在的作用方式。与赋形剂处理的糖尿病大鼠相比，口服20mg/kg体重的GLA-LA 10天可使空腹血糖浓度轻度降低（375±11 vs. 416±16mg/dl，p = 0.03），而空腹血浆胰岛素水平无变化。静脉注射胰岛素耐量试验后，GLA-LA、LA和GLA处理均可观察到外周胰岛素增敏作用，葡萄糖曲线下面积分别显著降低（p < 0.04）23%、13%和10%。这种作用与GLA-LA和LA处理的动物腓肠肌膜中葡萄糖转运蛋白4（GLUT4）蛋白含量分别增加67%和50%有关；然而单独GLA处理未观察到变化。有趣的是，GLA-LA和LA处理均纠正了糖尿病相关的腓肠肌低分子量还原型硫醇含量的降低。这些数据表明GLA-LA共轭物具有胰岛素增敏特性，其作用机制与其各成分相关，且与抗氧化作用有关。
