人源FGF-21在脂肪细胞糖代谢中的作用

近年来研究发现,成纤维细胞生长因子(FGF)-21是一种新的代谢调节因子.为了深入研究人源FGF-21（hFGF-21）的生物活性，本实验利用SUMO高效表达载体，高效表达成熟的hFGF-21，并利用小鼠3T3-L1脂肪细胞检测hFGF-21的糖代谢活性．实验结果表明，hFGF-21可促进脂肪细胞的葡萄糖吸收，且葡萄糖吸收效率呈剂量依赖性．hFGF-21作用4 h即可促进脂肪细胞糖吸收，其活性可持续24 h以上．hFGF-21与胰岛素共同作用的葡萄糖吸收效果，明显优于它们的单独作用结果，说明hFGF-21与胰岛素发挥协同作用．脂肪细胞经hFGF-21预处理后，显著增加了胰岛素促进脂肪细胞吸收葡萄糖的效率，说明hFGF-21可以增加胰岛素的敏感性．本实验为临床应用hFGF-21治疗糖尿病，增加胰岛素敏感性提供了依据．

Human Fibroblast Growth Factor-21 Regulates Glucose Uptake in 3T3-L1 Adipocytes

Recent discovery showed that fibroblast growth factor-21(FGF-21) is a new glucose regulator. To study the activity of human FGF-21(hFGF-21), we used SUMO His expression vector to efficiently express soluble hFGF-21 protein. To examine the glucose regulation activity of hFGF-21, 3T3-L1 pre-adipocytes were differentiated into adipocytes, glucose up-take activity of hFGF-21 was examined by glucose oxidase and peroxidase (GOD-POD) assay. The result showed that insulin could stimulate glucose uptake of 3T3-L1 adipocytes in a dose dependent manner, suggesting that the glucose-uptake assay is valid. The hFGF-21protein was subsequently tested in this system, the result showed that it can also stimulate glucose uptake of 3T3-L1 adipocytes in a dose-dependent manner. To examine effect of time on action of hFGF-21, 1　000nmol/L hFGF-21 was used to treat differentiated adipocytes for 4, 8, 20 and 24 hours, respectively, together with the same concentration of insulin and BSA as a positive and negative control. Glucose consumption of the medium was examined. The hFGF-21 started to show activity at 4 hours after treatment. The hFGF-21 activity last at least 24 hours. BSA did not show any glucose uptake activity as expected. We concluded that hFGF- 21 effect appeared to be insulin independent and additive to insulin activity upon co- administration. Glucose uptake by adipocytes stimulated with the mixture of hFGF-21 and insulin is better than either hFGF-21 or insulin alone. Furthermore，3T3-L1 adipocytes pretreated with hFGF-21 significantly increased sensitivity of the adipocytes to insulin treatment. These data provide evidence for clinic application of hFGF-21 and for treatment diabetes patients, and amelioration of insulin-resistance.