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Title 

Role of NADPH oxidase-4 in saturated fatty acid-induced insulin resistance in SK-Hep-1 cells

Authors 

J M OhJ M ChoiJ Y LeeSoo Jin OhB H KimS K Kim

Publisher 

Elsevier

Issue Date 

2014

Citation 

Food and Chemical Toxicology, vol. 63, no. 1, pp. 128-135

Keywords 

AktInsulin resistanceNOX4Reactive oxygen speciesStearic acid

Abstract 

We aimed to develop a cell culture model of type 2 diabetes by treating SK-Hep-1 cells with four free fatty acids [i.e., palmitic acid, stearic acid (SA), linoleic acid and oleic acid]. The results showed that Akt phosphorylation was increased in SK-Hep-1 cells treated with insulin in a time- and concentration-dependent manner, which was inhibited by saturated fatty acids, but not by unsaturated fatty acids. Moreover, protein levels of NADPH oxidase (NOX) 4 but not NOX2 were increased following SA treatment and, consequently, increased reactive oxygen species production and decreased cellular glutathione were observed. Apocynin, a NOX4 inhibitor, restored the SA-induced inhibition of Akt phosphorylation, suggesting the role of NOX4 in insulin resistance induced by SA. Neither phosphorylation level nor protein level of the stress signaling kinases, such as c-Jun N-terminal kinase or p38 mitogen activated protein kinase, was changed by SA treatment. Although binding immunoglobulin protein, a marker of endoplasmic reticulum stress, was transiently increased in SKHep-1 cells treated with SA, 4-phenyl butyric acid, a chemical chaperone, had no effect on the insulin-mediated Akt phosphorylation inhibited by SA. The present study provides a useful model for screening anti-insulin resistance drugs and finding new drug targets for treatment of diabetes.

ISSN 

0278-6915

Link 

http://dx.doi.org/10.1016/j.fct.2013.10.049

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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