成纤维细胞生长因子-21改善胰岛素抵抗肝细胞对葡萄糖的吸收及机制  

The effect of FGF-21 on the glucose uptakes and insulin resistance in cultured human liver cells

作　　者：李婷婷[1,2] 高丽昌[1,2] 唐禄 张健[1,2] 李富勇[2] 李海燕[1] 王晓杰[2,1] 李校堃[1,2] 

机构地区：[1]吉林农业大学生命科学学院,吉林长春130000 [2]温州医学院药学院,浙江温州325035 [3]浙江格鲁斯特生物科技有限公司,浙江温州325000

出　　处：《中国药理学通报》2012年第3期366-371,共6页Chinese Pharmacological Bulletin

基　　金：国家科技重大专项"重大新药创制"(No 2011ZX09102-004-03)

摘　　要：目的建立正常人肝细胞(HL-7702)胰岛素抵抗(in-sulin resistance,IR)模型,探讨成纤维细胞生长因子-21(FGF-21)对胰岛素抵抗的改善作用及其机制。方法培养HL-7702细胞,利用高浓度胰岛素和地塞米松(dexametha-sone,DEX)诱导IR模型。GOD-POD试剂盒测定细胞葡萄糖消耗量,Western blot检测GLUT1和磷酸化ERK1/2表达水平。结果 FGF-21促进HL-7702细胞葡萄糖的消耗且呈剂量依赖性,与胰岛素联合用药提高葡萄糖消耗量。在随后IR模型实验中,FGF-21改善IR模型细胞葡萄糖消耗量。FGF-21作用24 h,GLUT1的表达量明显增高,p-ERK1/2的含量增强。当加入ERK1/2特异性抑制剂PD98059,FGF-21促ERK1/2的磷酸化作用被抑制。IR模型中,FGF-21仍能提高p-ERK1/2的含量。结论 FGF-21促进HL-7702细胞对葡萄糖的消耗,改善IR HL-7702细胞葡萄糖消耗量,提高葡萄糖转运蛋白GLUT1和ERK1/2磷酸化的表达。Aim To establish an insulin resistance cell model and evaluate the effects of FGF-21 on insulin resistance.Methods Human liver cells were administrated by high concentration of Dexamethasone and insulin.Glucose uptake activity of FGF-21 was examined by glucose oxidase and peroxidase（GOD-POD） assay.The expressions of GLUT1 and the ERK1/2 signaling pathway were examined by Western blot.Results FGF-21 could stimulate glucose uptake of HL-7702 cells in a dose-dependent manner,suggesting that the glucose uptake assay was valid.Glucose uptake of HL-7702 cells stimulated by the mixture of FGF-21 and insulin was higher than that by FGF-21 or insulin solely.The FGF-21 protein was subsequently tested in IR cell models,showing that it could also stimulate glucose uptake of HL-7702 cells.The expressions of GLUT1 and the phosphorylation of ERK1/2 increased with the administration of FGF-21.The phosphorylation of ERK1/2 stimulated by FGF-21 was inhibited when PD98059,the specific inhibitor of ERK1/2,was added into the cell supernatant.In the IR model,FGF-21 could still increase the content of p-ERK1/2.Conclusions FGF-21 can stimulate glucose uptake of HL-7702 cells in a dose-dependent manner,and stimulate the glucose uptake of IR cell models.FGF-21 increases the expression of GLUT1 and the phosphorylation of ERK1/2.

关 键 词：FGF-21 肝细胞 地塞米松 胰岛素抵抗 GLUT1 ERK1/2信号 

分 类 号：R322.47[医药卫生—人体解剖和组织胚胎学] R343.23[医药卫生—基础医学]