Perfluorooctane sulfonate-induced insulin resistance is mediated by protein kinase B pathway.
Biochem Biophys Res Commun
; 477(4): 781-785, 2016 09 02.
Article
em En
| MEDLINE
| ID: mdl-27363333
ABSTRACT
Perfluorooctane sulfonate (PFOS), a persistent organic pollutant, is blamed to be associated with the incidence of insulin resistance in the general human population. In this study, we found that PFOS inhibited the phosphorylation and activation of protein kinase B (AKT), a key mediator of cellular insulin sensitivity, in human hepatoma HepG2 cells. The mRNA level of the gluconeogenic gene PEPCK, a downstream target gene of AKT, was increased in PFOS-treated cells. Due to stimulated gluconeogenesis, insulin-stimulated glucose uptake was decreased in HepG2 cells. In our previous study, we found that PFOS disturbed autophagy in HepG2 cells. We proposed that PFOS could inhibit the activation of AKT through inhibiting mTORC2, a key regulator of autophagy. In this study, we found that the levels of triglyceride were increased in HepG2 cells. PFOS-induced accumulation of hepatic lipids also contributed to the inhibition of AKT. Eventually, the inhibition of AKT led to insulin resistance in PFOS-treated cells. Our data would provide new mechanistic insights into PFOS-induced hepatic insulin resistance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Transdução de Sinais
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Ácidos Alcanossulfônicos
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Hepatócitos
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Proteínas Proto-Oncogênicas c-akt
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Fluorocarbonos
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Insulina
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2016
Tipo de documento:
Article