title: [The synergistic effect of FGF-21 and insulin on regulating glucose metabolism and its mechanism].
abstract: Previous studies proposed that the synergistic effect of fibroblast growth factor-21 (FGF-21) and insulin may be due to the improvement of insulin sensitivity by FGF-21. However, there is no experimental evidence to support this. This study was designed to elucidate the mechanism of synergistic effect of FGF-21 and insulin in the regulation of glucose metabolism. The synergistic effect of FGF-21 and insulin on regulating glucose metabolism was demonstrated by investigating the glucose absorption rate by insulin resistance HepG2 cell model and the blood glucose chances in type 2 diabetic db/db mice after treatments with different concentrations of FGF-21 or/and insulin; The synergistic metabolism was revealed through detecting GLUT1 and GLUT4 transcription levels in the liver by real-time PCR method. The experimental results showed that FGF-21 and insulin have a synergistic effect on the regulation of glucose metabolism. The results of real-time PCR showed that the effective dose of FGF-21 could up-regulate the transcription level of GLUT1 in a dose-dependent manner, but had no effect on the transcription level of GLUT4. Insulin (4 u) alone could up-regulate the transcription level of GLUT4, yet had no effect on that of GLUT1. Ineffective dose 0.1 mg kg(-1) FGF-21 alone could not change the transcription level of GLUT1 or GLUT4. However, when the ineffective dose 0.1 mg x kg(-1) FGF-21 was used in combination with insulin (4 u) significantly increased the transcription levels of both GLUT1 and GLUT4, the transcription level of GLUT1 was similar to that treated with 5 time concentration of FGF-21 alone; the transcription level of GLUT4 is higher than that treated with insulin (4 u) alone. In summary, in the presence of FGF-21, insulin increases the sensitivity of FGF-21 through enhancing GLUT1 transcription. Vice versa, FGF-21 increases the sensitivity of insulin by stimulating GLUT4 transcription in the presence of insulin. FGF-21 and insulin exert a synergistic effect on glucose metabolism through mutual sensitization.
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.forename: Cui-Yu
authors.initials: CY
authors.lastname: Sun
authors.forename: Guo-Peng
authors.initials: GP
authors.lastname: Sun
authors.forename: Gui-Ping
authors.initials: GP
authors.lastname: Ren
authors.forename: Xian-Long
authors.initials: XL
authors.lastname: Ye
authors.forename: Sheng-Long
authors.initials: SL
authors.lastname: Zhu
authors.forename: Wen-Fei
authors.initials: WF
authors.lastname: Wang
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Xu
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Ze-Shan
authors.initials: ZS
authors.lastname: Niu
authors.forename: Tian
authors.initials: T
authors.lastname: Sun
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Liu
authors.forename: De-Shan
authors.initials: DS
authors.lastname: Li
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004357:Drug Synergism; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D051379:Mice
chemical_list: D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D005947:Glucose