Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid thioctic acid - Participation of elements of the insulin signaling pathway
Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid thioctic acid - Participation of elements of the insulin signaling pathway
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DOI：
10.2337/diabetes.45.12.1798
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发表时间：
1996-12-01
期刊：
影响因子：
7.7
通讯作者：
Klip, A
中科院分区：
文献类型：
--
作者：
Estrada, DE;Ewart, HS;Klip, A
硫辛酸(α-硫辛酸)是脱氢酶复合体中的一种天然辅因子，在德国用于治疗糖尿病神经病变的症状。硫辛酸可改善大鼠肌肉制剂和在糖尿病患者进行的胰岛素钳夹研究中对胰岛素反应的葡萄糖利用。本研究的目的是确定硫辛酸对葡萄糖摄取和葡萄糖转运蛋白的直接影响。在培养的L6肌肉细胞和3T3-L1脂肪细胞中，(R)-硫辛酸能迅速增加葡萄糖摄取。这一增量高于S异构体或外消旋混合物引起的增量，与胰岛素引起的增量相当。在两种细胞中，与胰岛素作用平行的是，硫辛酸对葡萄糖摄取的刺激作用被磷脂酰肌醇3-激酶的抑制剂Wortmannin取消。硫辛酸引起葡萄糖摄取-胰岛素剂量-反应曲线上移。测定了两种细胞中GLUT1和GLUT4转运体的摩尔含量，发现3T3-L1脂肪细胞的葡萄糖转运体比L6肌管细胞多10倍，而GLUT4：Glut1的比例相似。本文研究了(R)-硫辛酸对L6肌管葡萄糖转运蛋白的影响。它对葡萄糖摄取的刺激作用与GLUT1和GLUT4葡萄糖转运体在细胞内的重新分布有关，与胰岛素的作用相似，对GLUT3转运体的影响很小。综上所述，硫辛酸刺激基础葡萄糖转运，并对胰岛素刺激的葡萄糖摄取有积极作用。这种刺激作用依赖于磷脂酰肌醇3-激酶的活性，并可能通过葡萄糖转运体的重新分布来解释。这是一种生理上相关的化合物可以通过胰岛素信号途径刺激葡萄糖运输的证据。
Thioctic acid (alpha-lipoic acid), a natural cofactor in dehydrogenase complexes, is used in Germany in the treatment of symptoms of diabetic neuropathy. Thioctic acid improves insulin-responsive glucose utilization in rat muscle preparations and during insulin clamp studies performed in diabetic individuals. The aim of this study was to determine the direct effect of thioctic acid on glucose uptake and glucose transporters. In L6 muscle cells and 3T3-L1 adipocytes in culture, glucose uptake was rapidly increased by (R)-thioctic acid. The increment was higher than that elicited by the (S)-isomer or the racemic mixture and was comparable with that caused by insulin. In parallel to insulin action, the stimulation of glucose uptake by thioctic acid was abolished by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, in both cell lines. Thioctic acid provoked an upward shift of the glucose-uptake insulin dose-response curve. The molar content of GLUT1 and GLUT4 transporters was measured in both cell lines, 3T3-L1 adipocytes were shown to have >10 times more glucose transporters but similar ratios of GLUT4:GLUT1 than L6 myotubes. The effect of (R)-thioctic acid on glucose transporters was studied in the L6 myotubes. Its stimulatory effect on glucose uptake was associated with an intracellular redistribution of GLUT1 and GLUT4 glucose transporters, similar to that caused by insulin, with minimal effects on GLUT3 transporters. In conclusion, thioctic acid stimulates basal glucose transport and has a positive effect on insulin-stimulated glucose uptake. The stimulatory effect is dependent on phosphatidylinositol 3-kinase activity and may be explained by a redistribution of glucose transporters. This is evidence that a physiologically relevant compound can stimulate glucose transport via the insulin signaling pathway.