title: Pharmacological efficacy of FGF21 analogue, liraglutide and insulin glargine in treatment of type 2 diabetes.
abstract: Fibroblast growth factor 21 (FGF21) is a promising regulator of glucose and lipid metabolism with multiple beneficial effects including hypoglycemic and lipid-lowering. Previous studies have reported that FGF21 is expected to become a new drug for treatment of diabetes. Liraglutide and insulin glargine are the two representative anti-diabetic biological drugs. In the current study, we aim to compare the long-term pharmacological efficacy of mFGF21 (an FGF21 analogue), liraglutide and insulin glargine in type 2 diabetic db/db mice. Db/db mice were initially treated with three kinds of proteins (25nmol/kg/day) by subcutaneous injection once a day for 4weeks, then subsequently be treated with once every two days for next 4weeks. After 8weeks of treatments, the blood glucose levels, body weights, glycosylated hemoglobin levels, fasting insulin levels, serum lipid profiles, hepatic biochemical parameters, oral glucose tolerance tests and hepatic mRNA expression levels of several proteins (GK, G6P, GLUT-1 and GLUT-4) associated with glucose metabolism of the experimental mice were detected. Results demonstrated that three proteins could significantly decrease the fed blood glucose levels of db/db mice. After treatment for 1week, the fed blood glucose levels of db/db mice in liraglutide group were significantly lower than those in mFGF21 and insulin glargine groups. However, after 2weeks of administration, the long-lasting hypoglycemic effect of mFGF21 was superior to liraglutide and insulin glargine up to the end of the experiments. Compared with liraglutide and insulin glargine, mFGF21 significantly reduced the glycosylated hemoglobin levels and improved the ability on glycemic control, insulin resistance, serum lipid and liver function states in db/db mice after 8weeks treatments. In addition, mFGF21 regulated glucose metabolism through increasing the mRNA expression levels of GK and GLUT-1, and decreasing the mRNA expression level of G6P. But liraglutide and insulin glargine could only up-regulate the mRNA expression of GLUT-4. In summary, as a hypoglycemic drug for long-term treatment, mFGF21 has the potential to be an ideal drug candidate for the therapy of type 2 diabetes.
authors.affiliation: College of Life Science, Henan Normal University, No. 46 construction road, 453007, Xinxiang, Henan Province, China. Electronic address: yexianlong1988@163.com.
authors.forename: Xianlong
authors.initials: X
authors.lastname: Ye
authors.affiliation: College of Life Science, Henan Normal University, No. 46 construction road, 453007, Xinxiang, Henan Province, China; Key Laboratory for Cell Differentiation Regulation, 453007, Xinxiang, Henan Province, China. Electronic address: qijianying616@163.com.
authors.forename: Jianying
authors.initials: J
authors.lastname: Qi
authors.affiliation: College of Life Science, Northeast Agricultural University, No. 59 Mucai Street, 150030, Harbin, Heilongjiang Province, China. Electronic address: 626319662@qq.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.affiliation: College of Life Science, Northeast Agricultural University, No. 59 Mucai Street, 150030, Harbin, Heilongjiang Province, China. Electronic address: 41139141@qq.com.
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Life Science, Northeast Agricultural University, No. 59 Mucai Street, 150030, Harbin, Heilongjiang Province, China. Electronic address: 490149835@qq.com.
authors.forename: Shenglong
authors.initials: S
authors.lastname: Zhu
authors.affiliation: College of Life Science, Northeast Agricultural University, No. 59 Mucai Street, 150030, Harbin, Heilongjiang Province, China. Electronic address: 272161384@qq.com.
authors.forename: Shujie
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Life Science, Northeast Agricultural University, No. 59 Mucai Street, 150030, Harbin, Heilongjiang Province, China. Electronic address: 904675454@qq.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: College of Life Science, Northeast Agricultural University, No. 59 Mucai Street, 150030, Harbin, Heilongjiang Province, China. Electronic address: renguiping@126.com.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.affiliation: College of Life Science, Northeast Agricultural University, No. 59 Mucai Street, 150030, Harbin, Heilongjiang Province, China. Electronic address: deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D015507:Drugs, Investigational / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000069036:Insulin Glargine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D000069450:Liraglutide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D050505:Mutant Proteins / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D015507:Drugs, Investigational; D007004:Hypoglycemic Agents; D050505:Mutant Proteins; D011994:Recombinant Proteins; C414620:fibroblast growth factor 21; D000069036:Insulin Glargine; D005346:Fibroblast Growth Factors; D000069450:Liraglutide; D010450:Endopeptidases
keywords: FGF21; Hypoglycemic effect; Insulin glargine; Liraglutide; Type 2 diabetes