乙酰左旋肉碱改善肿瘤坏死因子-α诱导大鼠L6细胞胰岛素抵抗的实验研究  

Effect of acetyl-L-carnitine on the insulin resistance of L6 cells induced by tumor necrosis factor-α

作　　者：张召锋[1] 赵明[1] 王军波[1] 丁叶[1] 戴小倩[1] 李勇[1] 

机构地区：[1]北京大学公共卫生学院营养与食品卫生学系,北京100191

出　　处：《卫生研究》2010年第2期152-154,共3页Journal of Hygiene Research

基　　金：国家"十一五"科技支撑计划项目(No.2006BAD28B01)

摘　　要：目的研究乙酰左旋肉碱(ALC)对肿瘤坏死因子α(TNF-α)诱导的大鼠肌细胞胰岛素抵抗的影响。方法分化好的L6肌细胞分为6组,分别为对照组、100nmol/L胰岛素组、100nmol/L胰岛素+10ng/ml TNF-α组、胰岛素+TNF-α+三个不同浓度ALC组(浓度分别为0.1、0.3、0.6mmol/L),继续培养24h。实验结束后分别用葡萄糖消耗实验、葡萄糖转运实验检测胰岛素刺激下L6细胞对葡萄糖的消耗和利用情况,Western blot检测细胞胰岛素受体底物-1(insulin receptor substrate-1,IRS-1)的蛋白表达水平。结果与100nmol/L胰岛素组比较,10ng/ml TNF-α作用24h后胰岛素刺激下细胞上清液中葡萄糖的残存量显著增加和细胞内葡萄糖转运量明显减少(P<0.05),而ALC作用后明显改善TNF-α的抑制作用(P<0.05),并呈剂量-反应关系。Western blot结果显示,与胰岛素组相比,TNF-α增高IRS-1的Ser307磷酸化表达,而ALC作用后减少IRS-1的Ser307磷酸化表达。结论10ng/ml TNF-α作用24h能诱导L6肌细胞的胰岛素抵抗,而ALC能改善这种胰岛素抵抗,可能是通过减少IRS-1的Ser307磷酸化表达来实现的。Objective To investigate the effects of acetyl-L-carnitine （ALC） on the insulin resistance of rat L6 cells induced by tumor necrosis factor-α （TNF-α）. Methods Well-differentiated rat L6 muscle cells were divided into 6 groups,including control group,insulin （100nmol /L） group,insulin （100nmol /L） ＋ TNF-α （10ng /ml） group,and three insulin ＋ TNF-α ＋ ALC （0. 1,0. 3 and 0. 6mmol /L respectively） groups. The glucose remained in culture medium was measured by the method of glucose oxidizes peroxides （ GOD-POD）. The glucose uptake of L6 cells was tested by [3 H]-2-deoxyglucose. The expression of insulin receptor substrate-1 （IRS-1） was examined by western blotting. Results The glucose content remained in culture medium was increased by TNF-α and the glucose uptake of cells was inhibited by TNF-α. The inhibition of TNF-α could be improved by ALC and in a dose- response relation. Compared with the insulin group,the expression of Ser307 phosphorylation of IRS-1 was lower in TNF-α group,and the expression of Ser307 phosphorylation of IRS-1 was decreased by ALC. Conclusion The insulin resistance in L6 cells induced by TNF-α might be attenuated by ALC via decreasing the expression of Ser307 phosphorylation of IRS-1.

关 键 词：乙酰左旋肉碱 肿瘤坏死因子Α 胰岛素抵抗 胰岛素受体底物-1 肿瘤 

分 类 号：R587.1[医药卫生—内分泌] R730.231[医药卫生—内科学]