FGF21 suppresses hepatic glucose production through the activation of atypical protein kinase Cι/λ.
Eur J Pharmacol
; 702(1-3): 302-8, 2013 Feb 28.
Article
em En
| MEDLINE
| ID: mdl-23305840
ABSTRACT
Fibroblast growth factor 21 (FGF21) has been identified as a potent and robust metabolic regulator. Administration of recombinant FGF21 protein to rodents and rhesus monkeys exerts strong anti-diabetic effects. Previous studies have demonstrated that FGF21 inhibits glucose output in the rat H4IIE hepatoma cell line. We performed pharmacological studies to investigate the mechanisms by which FGF21 regulates glucose production in these cells. We found that both insulin and FGF21 suppressed gene expression of G6Pase and PEPCK. Accordingly, glucose production was inhibited. The FGF21 effects were phosphoinositide 3-kinase (PI3K)-dependent, and, unlike insulin, Akt-independent. Additionally, we found that FGF21 induced PKCι/λ phosphorylation in a PI3K-dependent manner; and that a non-isoform selective PKC inhibitor blocked FGF21 inhibition of glucose production, while an inhibitor of classical and novel PKC isoforms had no effect on FGF21 inhibitory activity. Furthermore, hepatic PKCι/λ phosphorylation was upregulated in FGF21-treated diabetic db/db mice.These data support the proposition that FGF21 inhibits hepatic glucose production by the PI3K-dependent activation of PKCι/λ.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
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Fosfatidilinositol 3-Quinases
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Fatores de Crescimento de Fibroblastos
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Glucose
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Isoenzimas
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Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos