高糖磷酸化IKKβ Ser181诱导3T3-L1脂肪细胞胰岛素抵抗的分子机制  

Molecular mechanism of insulin resistance induced by high glucose in 3T3-L1 adipocytes through targeting IKKβ

作　　者：易屏[1] 陆付耳[2] 陈广[2] 徐丽君[2] 董慧[2] 王开富[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院中医科,武汉430030 [2]华中科技大学同济医学院附属同济医院中西医结合研究所,武汉430030

出　　处：《中国免疫学杂志》2009年第2期103-107,113,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金面上项目(30371816)资助

摘　　要：目的:探讨IKKβ及胰岛素信号转导分子在高糖诱导3T3-L1脂肪细胞胰岛素抵抗中的作用。方法:采用高糖加胰岛素诱导的胰岛素抵抗细胞模型,以2-脱氧-[3H]-D-葡萄糖摄入法观察葡萄糖的转运率,用Western blot检测IKKβ蛋白,IKKβ Ser181磷酸化,IRS-1蛋白,IRS-1Ser307磷酸化,PI-3Kp85蛋白及GLUT4蛋白的表达。结果:仅高糖加胰岛素模型组,胰岛素刺激的葡萄糖转运减少55%,同时IKKβ Ser181磷酸化、IRS-1Ser307磷酸化的表达显著增加,IRS-1蛋白和PI-3Kp85蛋白的表达显著减少,而IKKβ蛋白及GLUT4蛋白的表达无明显影响。结论:只有在胰岛素存在的条件下,高糖才可以诱导胰岛素抵抗,其分子机制可能与其激活IKKβSer181,使其下游的IRS-1和PI-3Kp85蛋白表达减少抑制葡萄糖转运有关,而与IKKβ蛋白及GLUT4蛋白的表达无关。Objective：To investigate the effects and molecular mechanisms of high glucose on insulin resistance in 3T3-L1 adipocytes. Methods： The model of insulin resistance in 3T3-L1 adipocytes was established by adding 25 mmol/L glucose with 0.6 nmo]/insulin to the culture medium. Glucose uptake rate was determined by 2-deoxy-[^3H]-D-glucose assay. The levels of IKKβ Ser181 phosphorylation, IRS-1Ser307 phosphorylation, the expression of IKKβ, IRS-1, NF-κB p65, PI-3K p85 and GLUT4 proteins were detected by Western blot assay. Resaltlts： After the intervention of 25 mmol/L glucose with 0.6 mmol/insulin for 18 h, the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 55% .Meanwhile,the expression of IRS-1 and PI-3K p85 protein was reduced while the levels of IKKβ Ser181 and IRS-1 Ser307 phosphorylation was increased,although the expression of GLUT4 and IKKβ was not changed. Condttsion： The results showed that only in the presence of 0.6 nmol/insulin, high contents of glucose can induce insulin resistance, the molecular mechanism of which might be that high glucose, by activating the phosphorylation of IKKβ Ser181, increases the phosphorylation of Set residue of IRS-1, thereby decreasing the phosphorylation of ganirnalon residue and regulating the expression of the signal protein of insulin-IRS-1 and PI-3K p85 to inhibit glucose uptake of 3T3-L1 adipocytes.

关 键 词：高糖 胰岛素抵抗 IKKΒ 3T3-L1脂肪细胞 

分 类 号：R392.6[医药卫生—免疫学]