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Pharmaceutical inactivation of Erk1/2 does not affect function of FGF21 to regulate glucose and lipid metabolic hemostasis / 中国病理生理杂志
Chinese Journal of Pathophysiology ; (12): 2212-2221, 2017.
Article in Chinese | WPRIM | ID: wpr-663024
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.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pathophysiology Year: 2017 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pathophysiology Year: 2017 Type: Article