棕榈酸通过抑制IRS-1表达诱导大鼠骨骼肌细胞胰岛素抵抗  

Palmitic Acid Induces Insulin Resistance in Rat Skeletal Muscle Cells by Down-regulating the Expression of IRS-1

作　　者：沈歆[1] 胡梓朔 王力彬[1] 周楠[1] 弥乐 刘雪英[1] 张生勇[1] 

机构地区：[1]第四军医大学药学院药物化学教研室,西安710032 [2]第四军医大学学员一旅

出　　处：《中国药师》2016年第12期2201-2205,共5页China Pharmacist

摘　　要：目的:建立L6细胞胰岛素抵抗模型,筛选出最佳诱导条件,并探讨其作用机制。方法:用MTT法确定棕榈酸、胰岛素对L6细胞增殖的影响;用葡萄糖检测试剂盒检测葡萄糖含量,确定不同浓度的棕榈酸、胰岛素对L6细胞葡萄糖消耗的影响;通过Western Blot法检测IRS-1、PI3K、P-AKT、AKT、GLUT4的蛋白表达。结果:0.4 mmol·L^(-1)棕榈酸诱导12 h、5×10^(-7)mol·L^(-1)胰岛素诱导24 h以上,对L6细胞生长无影响且出现明显胰岛素抵抗,移除刺激后24 h内能够抑制胰岛素刺激状态下的糖转运;棕榈酸降低了IRS-1、PI3K、P-AKT、GLUT4在L6细胞上的表达。结论:高浓度棕榈酸能够通过抑制IRS-1等靶蛋白表达诱导L6细胞产生胰岛素抵抗。Objective： To establish reliable insulin resistance of skeletal muscle cells model induced by palmitic acid for studying the mechanisms of insulin-resistance model and screening the best condition of its induction. Methods ： Identify the effect of PA or insulin on cell proliferation by MTT assay. The glucose concentration was measured by glucose oxidase and peroxidase （GOD-POD） method, and identify the effect of glucose consumption with different concentration of PA or insulin. The expression of IRS-1 ,PI3K,PAKT,AKT,GLUT4 in L6 cells were detected by Western Blot. Results： The insulin resistance model of L6 cells can be successful established by 12h incubated in cultured medium with 0.4 mmol ·L^-1 PA or 24h with 5 × 10^-7 mol ·L^-1 insulin. And insulin stimulated glucose transport was inhibited by 0.4 mmol ·L^-1 PA in L6 cells. Palmitic acid decreased IRS-1, PI3 K,P-AKT, GLUT4 expression in 1.6 cells. Conclusion： High concentration of palmitic acid may induce insulin resistance in L6 cells via inhibiting IRS-1 and PI3K- Akt signaling.

关 键 词：棕榈酸 大鼠骨骼肌细胞 胰岛素抵抗 胰岛素受体底物1 

分 类 号：R965.1[医药卫生—药理学]