Effect of tetrahydrocurcumin on insulin receptor status in type 2 diabetic rats: studies on insulin binding to erythrocytes
Effect of tetrahydrocurcumin on insulin receptor status in type 2 diabetic rats: studies on insulin binding to erythrocytes
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DOI：
10.1007/s12038-008-0022-y
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发表时间：
2008-03-01
影响因子：
2.9
通讯作者：
Rao, Chippada Appa
中科院分区：
文献类型：
--
作者：
Murugan, Pidaran;Pari, Leelavinothan;Rao, Chippada Appa
姜黄素是姜黄中最活跃的成分。人们认为姜黄素是一种有效的抗氧化剂和抗炎剂。四氢姜黄素（THC）是姜黄素的主要代谢产物之一，与姜黄素具有许多相同的生理和药理活性，在某些系统中可能比姜黄素发挥更大的抗氧化活性。以循环红细胞为细胞模型，研究了四氢大麻酚和姜黄素的胰岛素结合作用。以链脲佐菌素-烟酰胺诱导的雄性Wistar大鼠为实验模型。四氢大麻酚（80 mg/kg体重）口服45天。研究四氢大麻酚对血糖、血浆胰岛素及胰岛素与红细胞细胞膜受体结合的影响。糖尿病大鼠血浆胰岛素水平降低，胰岛素的平均特异性结合明显降低。这是由于平均胰岛素受体显著减少。与四氢大麻酚处理的糖尿病大鼠相比，糖尿病大鼠红细胞的胰岛素受体结合能力下降。Scatchard分析表明，胰岛素结合减少的原因是每个细胞的胰岛素受体位点减少，糖尿病大鼠的红细胞中每个细胞的胰岛素受体位点比四氢大麻酚处理的大鼠少。高亲和力（K-d1）、低亲和力（K-d2）和动力学分析显示，与糖尿病大鼠相比，四氢大麻酚处理大鼠红细胞的平均受体亲和力增加。这些结果提示糖尿病大鼠红细胞膜上胰岛素受体发生急性改变。四氢大麻酚治疗显著改善了胰岛素与受体的特异性结合，受体数量和亲和结合达到接近正常水平。我们的研究揭示了四氢大麻酚增加细胞总胰岛素结合位点数量导致血浆胰岛素显著升高的机制。四氢大麻酚的作用比姜黄素更显著。
Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin, and exhibits many of the same physiological and pharmacological activities as curcumin and, in some systems, may exert greater antioxidant activity than curcumin. Using circulating erythrocytes as the cellular mode, the insulin-binding effect of THC and curcumin was investigated. Streptozotocin (STZ)-nicotinamide-induced male Wistar rats were used as the experimental models. THC (80 mg/kg body weight) was administered orally for 45 days. The effect of THC on blood glucose, plasma insulin and insulin binding to its receptor on the cell membrane of erythrocytes were studied. Mean specific binding of insulin was significantly lowered in diabetic rats with a decrease in plasma insulin. This was due to a significant decrease in mean insulin receptors. Erythrocytes from diabetic rats showed a decreased ability for insulin-receptor binding when compared with THC-treated diabetic rats. Scatchard analysis demonstrated that the decrease in insulin binding was accounted for by a decrease in insulin receptor sites per cell, with erythrocytes of diabetic rats having less insulin receptor sites per cell than THC-treated rats. High affinity (K-d1), low affinity (K-d2) and kinetic analyses revealed an increase in the average receptor affinity of erythrocytes from THC-treated rats compared with those of diabetic rats. These results suggest that acute alteration of the insulin receptor on the membranes of erythrocytes occurred in diabetic rats. Treatment with THC significantly improved specific insulin binding to the receptors, with receptor numbers and affinity binding reaching near-normal levels. Our study suggests the mechanism by which THC increases the number of total cellular insulin binding sites resulting in a significant increase in plasma insulin. The effect of THC is more prominent than that of curcumin.