花生四烯酸改善饱和脂肪酸诱导肝细胞胰岛素抵抗的作用机制  

Mechanism of the ameliorative effect of arachidonic acid on saturated fatty acid-induced insulin resistance in HepG2 cells

作　　者：陈宝生[1] 万学东[1] 夏炎枝[1] 王西明[1] 

机构地区：[1]河南科技大学,河南洛阳471003

出　　处：《山东医药》2007年第28期1-3,共3页Shandong Medical Journal

基　　金：湖北省自然科学基金(2003ABA137);湖北省卫生厅科研项目(NX200403)

摘　　要：目的探讨花生四烯酸(AA)改善软脂酸(PA)诱导的肝细胞胰岛素抵抗(IR)的作用机制。方法分别用0.25 mmol/L PA和PA+50μmol/L AA与HepG2细胞共同培养24 h,并设正常对照组。测定每组在有无胰岛素刺激时及胰岛素刺激情况下加和不加入PI3K抑制剂WT或PKC抑制剂CC时细胞内糖异生限速酶磷酸烯醇式丙酮酸羧激酶(PEPCK)活性和胰岛素受体底物2(IRS-2)蛋白水平。结果PA组基础及胰岛素刺激的PEPCK活性比对照组和PA+AA组明显升高,IRS-2蛋白下降(P<0.05)。加入WT与否,对照组和PA+AA组PEPCK活性、IRS-2蛋白水平有明显差异(P<0.05);加入CC与否,对照组和PA+AA组IRS-2蛋白水平有明显差异(P<0.05);PA组均无变化。结论肝细胞IR时,胰岛素信号转导通路的PI3K途径和PKC通路可能存在严重障碍。AA通过纠正异常的糖代谢关键酶活性和胰岛素信号蛋白量,改善胰岛素信号转导通路缺陷,缓解PA引起的IR。[Objective] To study the mechanisms of ameliorative effects of arachidonic acid on saturated fatty acid-induced insulin resistance in HepG2 cells.[Methods] HepG2 cells were incubated in DMEM medium with 0.25 mmol/L palmitate（PA） and 0.25 mmol/L PA combined 50 μmol/L arachidonic acid（AA） for 24 hours respectively,normal group was taken as control.The activity of glyconeogenesis rate-limiting enzyme-phosphoenolpyruate carboxykinase（PEPCK） and insulin receptor substrate 2（IRS-2） protein level in cells were evaluated with or without insulin and PI3K inhibitor Wortmannin（WT）or PKC inhibitor-chelerythrine chloride（CC）.[Results] Basic and insulin induced PEPCK activities in PA group were higher than those of control group and PA＋AA group,IRS-2 protein level in PA group was lower than that of control group and PA＋AA group（P〈0.05）.Before and after WT intervention,PEPCK activity and IRS-2 protein level in control and PA＋AA group were statistically different（P〈0.05）;Before and after CC intervention,IRS-2 protein level in control group and PA＋AA group had obvious difference（P〈0.05）;there was no difference in PA group.[Conclusion] When hepatic cell was insulin resistant,insulin signal transduction iteral PT3K route and PKC route perhaps existed grave disorder.AA can improve insulin signal transduction iter defect and PA-induced insulin resistance by rectifying abnormal glycometabolism key enzyme activity and insulin signal protein level.

关 键 词：胰岛素抗药性 脂肪酸类 花生四烯酸 HEPG2细胞 

分 类 号：R587.1[医药卫生—内分泌]