title: Long-lasting anti-diabetic efficacy of PEGylated FGF-21 and liraglutide in treatment of type 2 diabetic mice.
abstract: Fibroblast growth factor-21 (FGF-21) is a new member of the FGF family and potential drug candidate for the treatment of type 2 diabetes mellitus. However, FGF-21 protein has short half-life in vivo, which severely affects its clinical application. In the present study, PEGylated FGF-21 was prepared by modifying the N-terminus of hFGF-21 with 20 kDa mPEG-ALD. The long-acting hypoglycemic effect of PEGylated FGF-21 and liraglutide was compared on type 2 diabetic db/db mice. The pharmacological efficacy of the compounds was evaluated by blood glucose levels, body weight, glycosylated hemoglobin levels, insulin levels, oral glucose tolerance test, lipid levels, and liver function parameters. We noticed that both PEGylated FGF-21 and liraglutide could significantly decrease plasma glucose in db/db mice. However, comparing to liraglutide treatments, PEGylated FGF-21 therapy resulted in more significant effect in lowering blood glucose levels and glycosylated hemoglobin levels, alleviating insulin resistance, improving lipid profile, liver function, and glucose control of the experimental mice. Our results suggest that PEGylated FGF-21 appears more beneficial anti-diabetic effect in type 2 diabetic mice than liraglutide, which holds significant promise as an ideal candidate for the treatment of type 2 diabetic patients.
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, No. 59 Mucai Street Xiangfang District, Harbin, 150030, Heilongjiang, People's Republic of China.
authors.forename: Xianlong
authors.initials: X
authors.lastname: Ye
authors.forename: Jianying
authors.initials: J
authors.lastname: Qi
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Wu
authors.forename: Shenglong
authors.initials: S
authors.lastname: Zhu
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.forename: Shujie
authors.initials: S
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Rasool Lubna
authors.initials: RL
authors.lastname: Muhi
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D000069450:Liraglutide / Q000494:pharmacology*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D005346:Fibroblast Growth Factors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D000069450:Liraglutide; D011092:Polyethylene Glycols; C414620:fibroblast growth factor 21