Long-acting hypoglycemic effects of PEGylated FGF21 and insulin glargine in mice with type 1 diabetes

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 28.0 mmol/L for the whole experiment, and the blood glucose of mice treated with insulin glargine remained at 16.5 to 18.0 mmol/L However, mice treated with PEG-FGF21 had lower blood glucose levels of 8.0 to 9.0 mmol/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. (C) 2015 Elsevier Inc. All rights reserved.