title: Efficacy of a combination of high and low dosage of PEGylated FGF-21 in treatment of diabetes in db/db mice.
abstract: 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 1.0mg/kg for 14days, then treated with pFGF-21 at maintenance doses of 0.125/0.250/0.375/0.500mg/kg for 30days. 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 0.125/0.250/0.375/0.500mg/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 0.125mg/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.
authors.affiliation: Biopharmaceutical Lab., School of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing, PR China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biopharmaceutical Lab., School of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Liying
authors.initials: L
authors.lastname: Song
authors.affiliation: Biopharmaceutical Lab., School of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Mir Hassan
authors.initials: MH
authors.lastname: Khoso
authors.affiliation: Biopharmaceutical Lab., School of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Li
authors.affiliation: Biopharmaceutical Lab., School of Life Science, Northeast Agricultural University, Harbin, PR China.
authors.forename: Xinghao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Xinxiang University, Xinxiang, PR China.
authors.forename: Jinjiao
authors.initials: J
authors.lastname: He
authors.affiliation: Institute of Biomedicine, Tasly Holding Group, Tianjin, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Pharmacology and Toxicology, Tasly Holding Group, Tianjin, PR China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ma
authors.affiliation: Biopharmaceutical Lab., School of Life Science, Northeast Agricultural University, Harbin, PR China. Electronic address: renguiping@126.com.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.affiliation: Biopharmaceutical Lab., School of Life Science, Northeast Agricultural University, Harbin, PR China. Electronic address: deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; C414620:fibroblast growth factor 21; D011092:Polyethylene Glycols; D005346:Fibroblast Growth Factors
keywords: Initial dose; Maintenance doses; PEGylated fibroblast growth factor-21; Type 2 diabetes