Iizuka Katsumi, Takeda Jun, Horikawa Yukio
Department of Diabetes and Endocrinology, Gifu University, Graduate School of Medicine, Gifu, Japan.
FEBS Lett. 2009 Sep 3;583(17):2882-6. doi: 10.1016/j.febslet.2009.07.053. Epub 2009 Aug 4.
Fibroblast growth factor 21 (FGF21) has beneficial effects of improving the plasma glucose and lipid profiles in diabetic rodents. Here, we investigated carbohydrate response element binding protein (ChREBP) involvement in the regulation of FGF21 mRNA expression in liver. Glucose stimulation and adenoviral overexpression of dominant active ChREBP increased FGF21 mRNA. Consistently, adenoviral expression of dominant negative Mlx inhibited glucose induction of FGF21 mRNA. Furthermore, deletion studies of mouse FGF21 gene promoter (-2000 to +65 bp) revealed a glucose responsive region between -74 and -52 bp. These findings suggest that FGF21 expression is regulated by ChREBP.
成纤维细胞生长因子21（FGF21）对改善糖尿病啮齿动物的血糖和血脂水平具有有益作用。在此，我们研究了碳水化合物反应元件结合蛋白（ChREBP）在肝脏中FGF21 mRNA表达调控中的作用。葡萄糖刺激和显性活性ChREBP的腺病毒过表达增加了FGF21 mRNA。同样，显性负性Mlx的腺病毒表达抑制了FGF21 mRNA的葡萄糖诱导。此外，对小鼠FGF21基因启动子（-2000至+65 bp）的缺失研究揭示了-74至-52 bp之间的葡萄糖反应区域。这些发现表明FGF21的表达受ChREBP调控。
