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Biochem Biophys Res Commun. 2016 Sep 2;477(4):781-785. doi: 10.1016/j.bbrc.2016.06.135. Epub 2016 Jun 27.

Perfluorooctane sulfonate-induced insulin resistance is mediated by protein kinase B pathway.

Author information

1
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
2
Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China.
3
Department of Occupational and Environmental Health, Dalian Medical University, 9 W Lushun South Road, Dalian 116044, PR China. Electronic address: yaoxiaofeng@dmu.edu.cn.

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.

KEYWORDS:

Human liver HepG2 cells; Insulin resistance; Perfluorooctane sulfonate; Protein kinase B; Triglyceride

PMID:
27363333
DOI:
10.1016/j.bbrc.2016.06.135
[Indexed for MEDLINE]

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