CAJ | 학술논문

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、 PI3K p85蛋白及Glu T4蛋白的表达.结果 0.3～1.0mmol/L PA 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Glu T4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PI3K p85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-3K p85蛋白表达减少抑制葡萄糖转运有关.
목적 연구유리지방산(FFA)대3T3-L1지방세포IKKβ급이도소신호전도단백적영향,탐토FFA유도이도소저항(IR)적분자궤제.방법 유도성숙적3T3-L1지방세포여0.3～1.0mmol/L적연지산(PA)배양6～24h,이2-탈양-[3H]-D-포도당섭입법관찰포도당적전운솔,용Western blot 검측IKKβ단백、IKKβ Ser181 린산화、IRS-1단백、IRS-1 Ser307 린산화、 PI3K p85단백급Glu T4단백적표체.결과 0.3～1.0mmol/L PA 작용6～24h후, 3T3-L1지방세포적포도당소모명현감소,동시,Western blot 현시,PA대IKKβ급Glu T4단백적표체무명현영향,각능명현증가IKKβ Ser181급IRS-1 Ser307 린산화,동시감소IRS-1 단백화PI3K p85단백적표체.결론 FFA가이유도IR,기분자궤제가능여FFA격활IKKβ ,사IRS-1사안산잔기린산화증가이락안산잔기린산화감소,진이사기하유적PI-3K p85단백표체감소억제포도당전운유관.
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-[3H]-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 Ser307 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 Ser 307 phosphorylation,the decreased protein expressions of PI-3K p85 and GLUT4.