中国病理生理杂志2017，Vol.33Issue(12)：2212-2221,10.DOI:10.3969/j.issn.1000-4718.2017.12.016
Erk1/2失活对FGF21调节糖脂代谢 调控的影响
Pharmaceutical inactivation of Erk1/2 does not affect function of FGF21 to regulate glucose and lipid metabolic hemostasis
摘要
Abstract
AIM: To investigate whether inactivation of extracellular signal-regulated kinase 1/2 ( Erk1/2 ) will affect the function of fibroblast growth factor 21 (FGF21) to regulate glucose and lipid metabolism .METHODS:Male db/db mice (8 weeks old) were treated with U0126 (an inhibitor of Erk1/2 kinase) for 1 week, and then treated with re-combinant human FGF21 protein and adenovirus-mediated FGF21 (Ad-FGF21).The profile changes of blood glucose and blood lipid were evaluated at 120 min or 4 weeks after FGF21 administration.Meanwhile, the molecular mechanism was ex-plored by in vitro study.RESULTS: Treatment of db/db mice with recombinant human FGF21 protein significantly re-duced blood glucose and triglyceride levels at 120 min after FGF21 administration , but these changes were comparable in U0126-treated mice .Furthermore , abnormal glucose and triglyceride levels , and glucose and insulin tolerance were strong-ly improved in db/db mice as accompanied with decreasing body fat content after 4 weeks of ad-FGF21 administration .In-terestingly, treatment with or without U0126 did not influence these effects of FGF21.Mechanically, treatment with Ad-FGF21 significantly upregulated the protein levels of p-Erk1/2 and peroxisome proliferator-activated receptor γ( PPARγ) as well as the expression of adiponectin at mRNA and protein levels in adipose tissues .However , treatment with or without U0126 did not change the profiles .On the other hand , in vitro experiments also indicated that treatment of adipocytes with recombinant human FGF 21 protein significantly activated Erk 1/2 phosphorylation , and upregulated the expression levels of PPARγand adiponectin (P<0.05).However, pre-administration of U0126 did not affect the profiles.CONCLUSION:Pharmaceutical inactivation of Erk 1/2 by U0216 does not affect the biological function of FGF 21 to regulate blood glucose balance and improve abnormal blood lipids in vivo.关键词
成纤维细胞生长因子21/细胞外信号调节激酶1/2/胰岛素增敏效应/糖脂代谢紊乱Key words
Fibroblast growth factor 21/Extracellular signal-regulated kinase 1/2/Insulin-sensitizing effect/Glucose and lipid metabolism disorder分类
医药卫生引用本文复制引用
吴朝明,郑巨佳,潘莹莹,叶艳娜,潘薛波,林灼锋..Erk1/2失活对FGF21调节糖脂代谢 调控的影响[J].中国病理生理杂志,2017,33(12):2212-2221,10.基金项目
国家自然科学基金资助项目(No.81471075) （No.81471075）
浙江省自然科学基金资助项目(No.LY15H070003) （No.LY15H070003）
