Yao Wen-Bing, Ren Gui-Ping, Han Yang, Cao Hong-Wei, Gao Hong-Mei, Kan Fang-Ming, Wang Qi, Li De-Shan
College of Life Science of Northeast Agricultural University, Harbin 150030, China.
Yao Xue Xue Bao. 2011 Jul;46(7):787-92.
FGF21 (fibroblast growth factor 21) is a recently described member of the FGF family. It has been previously demonstrated that FGF21 is a potent regulator of glucose homeostasis. To improve stability of FGF21 for better efficacy, a new form of recombinant FGF21 was generated by fusion of a full length FGF21 gene and the Fc fragment of human IgG4 with flexible linker sequence. To examine the glucose regulation activity of FGF21-L-Fc, 3T3-L1 pre-adipocytes were differentiated into adipocytes, and glucose uptake activity of FGF21-L-Fc was examined by glucose oxidase and peroxidase (GOD-POD) assay. The results showed that in comparison with wild type FGF21, FGF21-L-Fc was more potent in stimulation of glucose uptake by 3T3-L1. In vivo studies on the modified protein demonstrated that FGF-L-Fc had a better efficacy in lowering blood glucose of the STZ-induced diabetic animals and controlled glucose level for a longer time. The results provided a sound basis for further studies.
成纤维细胞生长因子21（FGF21）是成纤维细胞生长因子（FGF）家族中最近被描述的成员。先前已经证明，FGF21是葡萄糖稳态的有效调节因子。为了提高FGF21的稳定性以获得更好的疗效，通过将全长FGF21基因与具有柔性接头序列的人IgG4的Fc片段融合，产生了一种新形式的重组FGF21。为了检测FGF21-L-Fc的葡萄糖调节活性，将3T3-L1前脂肪细胞分化为脂肪细胞，并通过葡萄糖氧化酶和过氧化物酶（GOD-POD）测定法检测FGF21-L-Fc的葡萄糖摄取活性。结果表明，与野生型FGF21相比，FGF21-L-Fc在刺激3T3-L1摄取葡萄糖方面更有效。对该修饰蛋白的体内研究表明，FGF-L-Fc在降低链脲佐菌素诱导的糖尿病动物的血糖方面具有更好的疗效，并且能在更长时间内控制血糖水平。这些结果为进一步研究提供了坚实的基础。
