nNOS抑制剂对HepG2细胞胰岛素抵抗的影响  

Effects of nNOS inhibitors on insulin resistance in HepG2 cells

作　　者：赖冉 吕冬梅 鲁茜 王涛之 印晓星 LAI Ran;LYU Dongmei;LU Qian;WANG Tao;YIN Xiaoxing(Xuzhou Medical University, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou,Jiangsu 221004, China;Department of Pharmacy, the Affiliated Hospital of Xuzhou Medical University,Xuzhou, Jiangsu 221004)

机构地区：[1]徐州医科大学江苏省新药研究与临床药学重点实验室,江苏徐州221004 [2]徐州医科大学附属医院药学部,江苏徐州221004

出　　处：《徐州医科大学学报》2019年第6期424-428,共5页Journal of Xuzhou Medical University

基　　金：江苏省药学会-百特生物药学基金科研项目(201537);徐州市科技计划项目(KC15SH005)

摘　　要：目的采用高浓度胰岛素诱导HepG2细胞建立胰岛素抵抗模型,研究nNOS抑制剂Spermidine对胰岛素抵抗的影响,并探索这种相关性是否与IRS-2/PI3K/Akt信号通路有关。方法将HepG2细胞培养于胰岛素浓度为1×10^-6mol/L的培养液中16 h,采用葡萄糖氧化酶法检测细胞糖摄取量。待模型建立后,培养液中加入nNOS 抑制剂 Spermidine。比较对照组(Con组)、IR 组(1×10^-6mol/L胰岛素)、IR + Spermidine组(1×10^-6mol/胰岛素+ 1×10^-4 mol/L Spermidine)对IRS-2、PI3K、Akt蛋白表达量的影响。结果与Con组相比,Spermidine 组IRS -2、PI3K和Akt蛋白表达显著增加,差异具有统计学意义(P <0.05 );与Con组相比,IR组IRS - 2、PI3K 和Akt蛋白表达显著降低,差异具有统计学意义(P<0.05);与IR组相比,IR + Spermidine组IRS-2、PI3K和Akt 蛋白表达显著增加,差异具有统计学意义(P<0.05)。结论nNOS抑制剂可能通过IRS-2/PI3K/Akt信号通路改善HepG2细胞的胰岛素抵抗。Objective In this study, insulin resistance model was established by inducing HepG2 cells with high concentration of insulin in order to investigate the effect of nitric oxide synthase (nNOS) inhibitor spermidine on insulin resistance and to explore whether this correlation is related to insulin receptor substrate -2 (IRS -2)/ PBK/Akt signa ling pathway. Methods HepG2 cells were placed in the 1×10^-6mol/L insulin culture medium, and the glucose uptake kit was used to detect the eflect of the glucose uptake rate of HepG2 cells. After the model was established, the nNOS in hibitor spermidine was added into the culture medium. The effects of normal group ( Con group), IR group ((1×10^-6mol/L insulin) and IR + spermidine group (1×10^-6mol/L insulin + 1×10^-4 mol/L spermidine) on the expression of IRS -2, PI3K and Akt protein were compared. Results The expression of IRS -2, PI3K and Akt protein in Spermidine group was significantly higher than that in Con group (P<0.05). Compared with Con group, the expression of IRS-2, PI3K and Akt protein in IR group decreased significantly (P <0.05). Compared with IR group, the expression of IRS - 2, PI3K and Akt protein in IR + Spermidine group increased significantly (P <0.05). Conclusions nNOS inhibitors may improve insulin resistance of HepG2 cells through IRS -2/PI3K/Akt signaling pathway.

关 键 词：糖尿病 一氧化氮合酶抑制剂 胰岛素抵抗 

分 类 号：R915[医药卫生—微生物与生化药学]