title: Insulin sensitizes FGF21 in glucose and lipid metabolisms via activating common AKT pathway.
abstract: Previous studies reveal that fibroblast growth factor 21 (FGF21) sensitizes insulin to achieve a synergy in regulating glucose metabolism. Here, we report that insulin sensitizes FGF21 in regulating both glucose and lipid metabolisms. db/db diabetic mice were subcutaneously administrated once a day for 6 weeks. Effective dose of insulin (1 U) could control blood glucose level of the db/db mice for maximum of 2 h, increased the body weight of the db/db mice and did not improve serum lipid parameters. In contrast, effective dose of FGF21 (0.5 mg/kg) could maintain blood glucose of the db/db mice at normal level for at least 24 h, repressed the weight gain of the mice and significantly improved lipid parameters. Ineffective doses of FGF21 (0.125 mg/kg) and insulin had no effect on blood glucose level of the db/db mice after 24 h administration, body weight or lipid parameters. However, combination of the two ineffective doses could maintain blood glucose level of the db/db mice for at least 24 h, suppressed weight gain and significantly improved lipid parameters. These results suggest that insulin sensitizes FGF21 in regulating both glucose and lipid metabolism. The results aimed to study the molecular basis of FGF21 sensitization indicates that combination of the two ineffective doses increased the mRNA expression of glut1, glut4, β-Klotho, sirt1, pgc-1α, ucp-1 and AKT phosphorylation, decreased fasn. The results demonstrate that insulin sensitizes FGF21 through elevating the phosphorylation of common gene Akt and amplifying FGF21 downstream signaling, including increasing expression of glut1 sirt1, pgc-1α, ucp-1, and decreasing fasn expression. In summary, we reports herein for the first time that insulin sensitizes FGF21 to achieve a synergy in regulating glucose and lipid metabolism. Along with previous studies, we conclude that the synergistic effect between FGF21 and insulin is realized through mutual sensitization.
authors.affiliation: Biopharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.affiliation: School of Life Science, Henan Normal University, Xinxiang, 453007, China.
authors.forename: Xianlong
authors.initials: X
authors.lastname: Ye
authors.affiliation: Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Biopharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Li
authors.affiliation: Biopharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Yongbi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Biopharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Jinjiao
authors.initials: J
authors.lastname: He
authors.affiliation: Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Yunye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Biopharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Biopharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Biopharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, China. deshanli@163.com.|Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, 150030, China. deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
authors.affiliation: Biopharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin, 150030, China. renguiping@163.com.|Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, 150030, China. renguiping@163.com.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004357:Drug Synergism; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051058:Oncogene Protein v-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D051058:Oncogene Protein v-akt; D005947:Glucose
keywords: AKT; Fibroblast growth factor21(FGF21); Glucose and lipid metabolism; Insulin