游离脂肪酸诱导3T3-L1脂肪细胞胰岛素抵抗的分子机制  

Molecular mechanism of insulin resistance induced by FFAs in 3T3-L1 adipocytes through activating IKKβ

作　　者：易屏[1] 陆付耳 陈广 徐丽君 王开富 

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430032 [2]中西结合研究所

出　　处：《中国糖尿病杂志》2008年第4期221-224,共4页Chinese Journal of Diabetes

基　　金：国家自然科学基金(30371816)

摘　　要：目的研究游离脂肪酸（FFA）对3T3-L1脂肪细胞IKKβ及胰岛素信号转导蛋白的影响,探讨FFA诱导胰岛素抵抗（IR）的分子机制。方法诱导成熟的3T3-L1脂肪细胞与0.3-1.0mmol/L的软脂酸（PA）培养6-24h,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-1 Ser307磷酸化、PI3Kp85蛋白及GluT4蛋白的表达。结果0.3-1.0mmol/LPA作用6-24h后,3T3-L1脂肪细胞的葡萄糖消耗明显减少,同时,Western blot显示,PA对IKKβ及GluT4蛋白的表达无明显影响,却能明显增加IKKβ Ser181及IRS-1 Ser307磷酸化,同时减少IRS-1蛋白和PI3Kp85蛋白的表达。结论FFA可以诱导IR,其分子机制可能与FFA激活IKKβ,使IRS-1丝氨酸残基磷酸化增加而酪氨酸残基磷酸化减少,进而使其下游的PI-3Kp85蛋白表达减少抑制葡萄糖转运有关。Objective To investigate the effect of FFAs on expression and activity of IKKβ and the signal protein of insulin in 3T3-L1 adipocytes and the possible molecular mechanism for insulin resistance. Methods 3T3-L1 adipocytes were treated for 6-24h with palmic acid to induce insulin resistance. The 2- deoxy-P HI-D-glucose method was used for the determination of glucose uptake rate. Western blot was used for the determinations of IKKβ Ser181 phosphorylation, IRS-1 Set307 phosphorylation, the protein expressions of IKKβ, IRS-1, PI3K p85 and GluT4. Results After the treatment with 0. 3-1.0 mmol/L of palmic acid for 6-24 h, the insulin-stimulated glucose transport of 3T3-L1 adipose cells were decreased in a dose- and time-dependent manner; IRS-1 and PI3K p85 protein decreased gradually. But GluT4 and IKKβ protein abundance showed no change during this study. Conclusions FFAs-induced insulin resistance may be correlated with an IKKβ activation, the increased IRS-1 Set 307 phosphorylation, the decreased protein expressions of PI-3K p85 and GLUT4.

关 键 词：游离脂肪酸 胰岛素抵抗 IKKΒ 

分 类 号：R587.1[医药卫生—内分泌]