当前位置: X-MOL 学术Toxicol. Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Changes in glucose metabolism and mRNA expression of IRS-2 in rats exposed to phoxim and the protective effects of vitamin E†
Toxicology Research ( IF 2.2 ) Pub Date : 2017-12-01 00:00:00 , DOI: 10.1039/c7tx00243b
Jing Zhang 1 , Wentao Song 1 , Yuecheng Sun 1 , Baojing Cheng 1 , Anshan Shan 1
Affiliation  

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−1) and VE (200 mg kg−1) were administered orally to Sprague-Dawley rats over a period of 28 consecutive days. After exposure to phoxim, the animals showed glucose intolerance and hyperinsulinemia during glucose tolerance tests, and insulin tolerance tests demonstrated an impaired glucose-lowering effect of insulin. Phoxim increases the fasting glucose, insulin and cholesterol levels, as well as the liver hexokinase activity (HK) significantly while decreasing the high density lipoprotein (HDL) cholesterol, and glycogen content in the liver and skeletal muscles observably. Furthermore, we observed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices. The insulin receptor substrate (IRS)-2 mRNA expressions of liver and skeletal muscles 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 in hepatocytes and muscles. VE supplementation reduced the fasting glucose, increased the glycogen content and HDL-cholesterol, but did not reduce the insulin resistance indices, when phoxim-treated rats were compared to VE supplemented rats. Overall, this study shows that vitamin E modifies the phoxim toxicity in rats only to a moderate degree.

中文翻译:


辛硫磷暴露大鼠葡萄糖代谢和 IRS-2 mRNA 表达的变化以及维生素 E 的保护作用†



研究表明,有机磷农药会损害葡萄糖稳态,导致胰岛素抵抗和 2 型糖尿病。目前的研究调查了辛硫磷对胰岛素信号通路的影响以及维生素 E 的保护作用。在 28 天内,给 Sprague-Dawley 大鼠口服辛硫磷 (180 mg kg -1 ) 和 VE (200 mg kg -1 )。连续几天。接触辛硫磷后,动物在糖耐量试验中表现出葡萄糖不耐症和高胰岛素血症,而胰岛素耐量试验则显示胰岛素的降糖作用受损。辛硫磷显着增加空腹血糖、胰岛素和胆固醇水平以及肝脏己糖激酶活性(HK),同时显着降低高密度脂蛋白(HDL)胆固醇以及肝脏和骨骼肌中的糖原含量。此外,我们观察到胰岛素抵抗生物标志物增加和胰岛素敏感性指数下降。辛硫磷下调肝脏和骨骼肌胰岛素受体底物(IRS)-2 mRNA表达,而IRS-1表达无差异。用辛硫磷处理后,甘油三酯、低密度脂蛋白胆固醇和空腹血糖没有差异。根据生化和分子研究结果,辛硫磷已被确定通过胰岛素抵抗和胰岛素信号通路破坏而损害葡萄糖稳态,从而导致肝细胞和肌肉中胰岛素的功能降低。当辛硫磷处理的大鼠与补充 VE 的大鼠进行比较时,VE 补充降低了空腹血糖,增加了糖原含量和 HDL-胆固醇,但没有降低胰岛素抵抗指数。 总体而言,这项研究表明维生素 E 仅在中等程度上改变了辛硫磷对大鼠的毒性。
更新日期:2017-12-01
down
wechat
bug