重组人成纤维细胞生长因子21降糖作用研究  

The studies on hypoglycemic effect of rhFGF21 both in vitro and in vivo

作　　者：张健[1,2,3,4] 李婷婷[1,2,3] 唐禄 田海山[2,4] 林灼峰[2] 李海燕[1] 王晓杰[1,2,4] 李校堃[1,2,4] 

机构地区：[1]吉林农业大学生物反应器与药物开发教育部工程研究中心,吉林长春130021 [2]温州医学院药学院,浙江温州325035 [3]吉林农业大学生命科学学院,吉林长春130021 [4]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5期632-636,共5页Chinese Pharmacological Bulletin

基　　金：科技部"重大新药创制"科技重大专项(No 2011ZX09102-004-03);浙江省科技厅重点项目(No 2009C13040)

摘　　要：目的利用肝细胞、肌肉细胞,前脂肪细胞及ob/ob小鼠进行rhFGF21体内外降糖作用研究。方法培养人正常肝细胞(HL-7702),大鼠肌肉细胞(L-6),小鼠前脂肪细胞(3T3-L1),用GOD-POD试剂盒测定细胞葡萄糖吸收量;FGF-21按照每天0.6μg·g-1的剂量颈部皮下连续注射7d,分别在d 0、d 3、d 7给药后1 h检测空腹血糖,以生理盐水做对比;rhFGF-21按照每天0.6μg·g-1的剂量颈部皮下连续注射9 d,末次给药后1 h开始口服糖耐量实验,灌胃给予2 mg.g-1的葡萄糖溶液,分别于给予葡萄糖溶液后30、60、120 min检测血糖;rhFGF-21按照每天2.5μg·g-1的剂量颈部皮下注射连续7 d,在d 0、d 3、d 7给药后1 h检测餐后血糖。结果在3.9 mg·L-1～100 mg·L-1间rhFGF21促进HL-7702细胞葡萄糖的吸收且呈现浓度-效应关系,与对照组相比差异有显著性(P<0.01);在0.3 mg·L-1～250 mg·L-1间rhFGF21促进L6肌细胞对葡萄糖的吸收,与对照组相比差异有显著性(P<0.05);在12.6 mg·L-1～100 mg·L-1间rhFGF21促进分化的3T3-L1细胞葡萄糖的吸收且呈现浓度-效应关系,与对照组相比差异有显著性(P<0.05);ob/ob小鼠血糖测试证明,rhFGF-21具有降血糖和改善葡萄糖耐受量的作用。结论 rhFGF21体外可促进肝细胞、肌肉细胞及脂肪细胞葡萄糖的吸收;rhFGF-21可降低ob/ob小鼠空腹血糖及餐后血糖,具有改善其葡萄糖耐受量的作用。Aim To study the hypoglycemic effect of rhFGF21 in vitro and in vivo by using liver cells,muscle cells,preadipocytes and ob/ob mice.Methods GOD-POD kits were used for determination of cellular glucose uptake in normal human liver cell line（HL7702）,rat muscle cell line（L-6）,and mouse preadipocytes（3T3-L1）;rhFGF-21 was subcutaneously and continuously injected,at the dose of 0.6 μg·g-1 per day,for 7 days,and the levels of fasting blood glucose on day 0,3 and 7 after administration were recorded and compared to those of the saline-treated control;rhFGF-21 was subcutaneously and continuously injected,at the dose of 0.6 μg·g-1 per day,for 9 days.Oral glucose tolerance test was done 1 h after the last administration.Briefly,glucose solution was administered intragastrically at the dose of 2 mg.g-1,and the concentration of blood glucose was detected 30 min,60 min,120 min after glucose administration;rhFGF-21 was subcutaneously and continuously injected,at the dose of 2.5 μg·g-1 per day,for 7 days,and postprandial blood glucose concentrations were detected on day 0,3,and 7 after the administration.Results rhFGF21 at the concentration of 3.9 mg·L-1～100 mg·L-1 significantly promoted glucose absorption in HL7702 cells in a dose-dependent manner（P0.01）;rhFGF21 at the dose of 0.3 mg·L-1～250 mg·L-1 significantly increased glucose consumption in L6 muscle cells（P0.05）;rhFGF21 at the dose of 12.6 mg·L-1～100 mg·L-1 significantly promoted the glucose absorption in differentiated 3T3-L1 cells in a dosedependent manner（P0.05）;in vivo blood glucose experiment showed that rhFGF-21 treatment greatly reduced blood glucose concentration and improved glucose tolerance in ob/ ob mice.Conclusions rhFGF21 treatment increases glucose absorption in liver cells,muscle cells and adipose cells;rhFGF-21 treatment also reduces fasting and postprandial blood glucose concentration in ob/ ob mice,exhibiting its function of improving the amount of glucose tolerance.

关 键 词：FGF-21 降糖作用 肝细胞 肌肉细胞 前脂肪细胞 OB/OB小鼠 

分 类 号：R-332[医药卫生] R329.2