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Changes in glucose metabolism and mRNA expression of IRS-2 in rats exposed to phoxim and the protective effects of vitamin E

Abstract

Research has shown that organophosphorus pesticides impair glucose homeostasis and cause insulin resistance and type 2 diabetes. The current study investigates the influence of phoxim on insulin signaling pathways and the protective effects of Vitamin E. Phoxim (180 mg/kg) and VE (200 mg/kg) were administered orally to Sprague-Dawley rats over a period of 28 consecutive days. After exposure to phoxim, the animals displayed glucose intolerance and hyperinsulinemia during glucose tolerance tests, and insulin tolerance tests demonstrated an impaired glucose-lowering effect of insulin. Phoxim increases fasting glucose, insulin and cholesterol levels, as well as liver hexokinase activity (HK) significantly. While decrease the high density lipoprotein (HDL) cholesterol, glycogen content in the liver and skeletal muscles observably. Further, we observed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices. The insulin receptor substrates (IRS)-2 mRNA expressions of liver and skeletal muscle were down regulated by phoxim, while the expression of IRS-1 showed no difference. There were no differences in triglycerides, LDL-cholesterol, and fasting glucose treated with phoxim. On the basis of biochemical and molecular findings, phoxim has been determined to impair glucose homeostasis through insulin resistance and insulin signaling pathway disruptions resulting in a reduced function of insulin into hepatocytes and muscle. VE supplementation reduced fasting glucose, increased glycogen content and HDL-cholesterol, but did not reduce insulin resistance indices, when phoxim treated rats were compared to VE supplemented rats. Overall, this study shows that vitamin E only phoxim toxicity in rats to a moderate degree modifies.

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Publication details

The article was received on 11 Sep 2017, accepted on 22 Nov 2017 and first published on 01 Dec 2017


Article type: Paper
DOI: 10.1039/C7TX00243B
Citation: Toxicol. Res., 2017, Accepted Manuscript
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    Changes in glucose metabolism and mRNA expression of IRS-2 in rats exposed to phoxim and the protective effects of vitamin E

    J. Zhang, W. Song, Y. Sun, B. Cheng and A. Shan, Toxicol. Res., 2017, Accepted Manuscript , DOI: 10.1039/C7TX00243B

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