title: Long-acting hypoglycemic effects of PEGylated FGF21 and insulin glargine in mice with type 1 diabetes.
abstract: OBJECTIVE
  In this study, we compared the long-acting hypoglycemic effect of PEGylated FGF21 (PEG-FGF21) with insulin glargine in mice with STZ-induced type 1 diabetes.
  
  
  METHODS
  PEG-FGF21 and insulin glargine were administered once daily for two months, and blood glucose was measured prior to the next administration. Real-time PCR was used to measure mRNA expression of glucokinase (GK), glucose 6-phosphatase (G6pase), phosphoenolpyruvate carboxykinase (PEPCK), glucose transporter 1 (GLUT1) and glucose transporter 4 (GLUT4).
  
  
  RESULTS
  During long-term treatment, the blood glucose of untreated mice remained at 25.0 to 28.0mmol/L for the whole experiment, and the blood glucose of mice treated with insulin glargine remained at 16.5 to 18.0mmol/L. However, mice treated with PEG-FGF21 had lower blood glucose levels of 8.0 to 9.0mmol/L on day 10 and maintained this level until the end of the experiment. qRT-PCR showed that PEG-FGF21 up-regulated mRNA expression of GK and GLUT1, and down-regulated mRNA expression of G6Pase and PEPCK. Insulin glargine up-regulated mRNA expression of GLUT4, but had no effect on GK, G6Pase, PEPCK or GLUT1.
  
  
  CONCLUSIONS
  PEG-FGF21 has a better long-acting efficacy than insulin glargine. PEG-FGF21 achieves glucose clearance by accelerating glycolysis by up-regulating expression of GK and GLUT1 and inhibiting gluconeogenesis via down-regulation of G6Pase and PEPCK expression.
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China.
authors.forename: Xianlong
authors.initials: X
authors.lastname: Ye
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China. Electronic address: renguiping@126.com.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, China; Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, P.R. China. Electronic address: deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000069036:Insulin Glargine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011092:Polyethylene Glycols / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D013311:Streptozocin; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; C414620:fibroblast growth factor 21; C039441:insulin, polyethylene glycol(B1)-; D000069036:Insulin Glargine; D011092:Polyethylene Glycols; D013311:Streptozocin; D005346:Fibroblast Growth Factors
keywords: Gluconeogenesis; Glycolysis; Insulin glargine; Long-acting hypoglycemic effects; PEGylated FGF21; Type 1 diabetic mice