二甲双胍对正常饮食大鼠血清成纤维细胞生长因子19、21及胰腺成纤维细胞生长因子受体1的影响

Effects of metformin on FGF19 and FGF21 and pancreatic FGFR1 in normal diet male rats

目的探讨二甲双胍(METF)对血清成纤维细胞生长因子(FGF)19和FGF21及胰腺成纤维细胞生长因子受体(FGFR)1和Akt通路上分子的影响。方法给予8周龄健康雄性Wistar大鼠(40只)标准饮食,随机分为正常对照(Con)组和METF(500 mg·kg^(-1)·d^(-1))。在24 w末检测血清生化学指标及FGF19和FGF21水平。蛋白免疫印迹检测胰腺组织FGFR1,Akt、磷酸化的Akt(p-Akt),FoxO1、磷酸化的FoxO1(p-FoxO1)的表达水平。结果 METF干预可以减轻大鼠的体重,降低大鼠空腹血糖、低密度脂蛋白和胆汁酸水平。METF组大鼠血清FGF21较Con组明显升高(P<0.05),而FGF19较Con组明显减低(P<0.05)。此外,胰腺FGFR1的表达水平及Akt及FoxO1的磷酸化水平在METF干预后明显升高(均P<0.05)。结论 METF可以降低血清FGF19、升高血清FGF21水平,对两者产生相反的作用。此外,METF可能通过增加FGFR1的表达、Akt及FoxO1的磷酸化对胰腺功能产生影响。

Objective To examine metformin＇s effects on FGF19 and FGF21 serum levels as well as pancreatic FGFR1 protein levels.Methods 40 male Wistar rats were randomly assigned to control group（ Con） and metfromin group（ METF） with or without metformin treatment（ 500 mg·kg^（-1）·d^（-1））.Biochemical parameters and serum FGF19 and FGF21 levels were evaluated after 24 weeks intervention.Pancreatic tissues were collected to assess FGFR1,Akt and FoxO1 protein levels by Western blot.Results Metformin reduced body weight,fasting plasma glucose（ FPG）,low-density lipoprotein cholesterol（ LDL-C） and total bile acids（ TBAs） levels compared to those of Con group.Besides,serum FGF21 level was higher and FGF19 level was lower in METF rats. Moreover,protein levels of pancreatic FGFR1,phosphorylated Akt（ p-Akt） and phosphorylated-FoxO1（ p-FoxO1） were significantly increased in METF rats. Conclusions Metformin might have an impact on beta cells by increasing protein levels of FGFR1,p-Akt and p-FoxO1.