人源FGF-21在脂肪细胞糖代谢中的作用  

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

作　　者：李晋南[1] 刘铭瑶[1] 侯玉婷[1] 任桂萍[1] 高华山[1] 张振宇[1] 李德山[1] 

机构地区：[1]东北农业大学生命科学学院生物制药教研室,哈尔滨150030

出　　处：《中国生物化学与分子生物学报》2009年第6期556-562,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：黑龙江省科技厅重点攻关项目(No.2006G0461-00)~~

摘　　要：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4h即可促进脂肪细胞糖吸收,其活性可持续24h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.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-adipoeytes 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.

关 键 词：成纤维细胞生长因子-21 糖代谢 脂肪细胞3T3-L1 胰岛素抵抗 

分 类 号：Q71[生物学—分子生物学]