Pharmaceutical inactivation of Erk1/2 does not affect function of FGF21 to regulate glucose and lipid metabolic hemostasis
10.3969/j.issn.1000-4718.2017.12.016
- VernacularTitle:Erk1/2失活对FGF21调节糖脂代谢 调控的影响
- Author:
ming Chao WU
1
;
jia Ju ZHENG
;
ying Ying PAN
;
na Yan YE
;
bo Xue PAN
;
feng Zhuo LIN
Author Information
1. 温州医科大学 附属第二医院
- Keywords:
Fibroblast growth factor 21;
Extracellular signal-regulated kinase 1/2;
Insulin-sensitizing effect;
Glucose and lipid metabolism disorder
- From:
Chinese Journal of Pathophysiology
2017;33(12):2212-2221
- CountryChina
- Language:Chinese
-
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.
