Efficacy of a combination of high and low dosage of PEGylated FGF-21 in treatment of diabetes in db/db mice

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• 作者：Pengfei Xu^a ; Yingjie Zhang^b ; Liying Song^a ; Mir Hassan Khoso^a ; Junyan Li^a ; Xinghao Jiang^a ; Jinjiao He^c ; Jian Li^d ; Xiaohui Ma^e ; Guiping Ren^a ; ^{renguiping@126.com} ; Deshan Li^a ; ^{deshanli@163.com}
• 关键词：PEGylated fibroblast growth factor-21 ; Type 2 diabetes ; Initial dose ; Maintenance doses
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：84
• 期：Complete
• 页码：97-105
• 全文大小：1832 K
• 卷排序：84

文摘

The aim of this study is to explore a new method—high dose starting and low dose maintaining for PEGylated Fibroblast growth factor 21 (pFGF-21) treatment. Db/db mice were initially treated with pFGF-21 of high dose, then treated with pFGF-21 of low doses. The mice were treated with pFGF-21 at initial dose of 1.0 mg/kg for 14 days, then treated with pFGF-21 at maintenance doses of 0.125/0.250/0.375/0.500 mg/kg for 30 days. The hypoglycemic and hypolipidemic effects of pFGF-21 of different maintenance doses were compared. The pharmacological efficacy of the maintenance doses of pFGF-21 was evaluated by blood glucose levels, oral glucose tolerance test, glycosylated hemoglobin levels, insulin levels, body weight, lipid profile parameters, the mRNA expressions of glycolysis-related genes, the mRNA expressions of gluconeogenesis-related genes and the mRNA expressions of lipid metabolism-related genes. Results showed that in comparison to the mice treated only with initial dose, the treatment with pFGF-21 at maintenance doses of 0.125/0.250/0.375/0.500 mg/kg exhibited favorable efficacy in lowering blood glucose levels and glycosylated hemoglobin levels, thus alleviating insulin resistance and improving dyslipidemia. However, among all of the maintenance doses, the dose of 0.125 mg/kg was less effective than the other maintenance doses. These results suggest that using the treatment method of high dose of PEGylated FGF-21 in the start and low dose maintaining results in favorable control of the glycolipid metabolic balance. This study provides a new method for PEGylated FGF-21 treatment which is beneficial to promote the clinical application of PEGylated FGF-21.