Sun Quancai, Peng Ye, Qi Weipeng, Kim Yoo, Clark John M, Kim Daeyoung, Park Yeonhwa
Department of Food Science, United States.
Department of Veterinary and Animal Sciences, United States.
Food Chem Toxicol. 2017 Nov;109(Pt 1):95-101. doi: 10.1016/j.fct.2017.08.046. Epub 2017 Sep 1.
Previously 10 μM permethrin (38.7% cis and 59.4% trans isomers), a pyrethroid insecticide widely used in agriculture and household products for pest control, was reported to reduce insulin-stimulated glucose uptake and phosphorylation of protein kinase B (p-AKT) in C2C12 mouse myotubes. The underlying mechanisms on how permethrin decreases insulin-stimulated AKT phosphorylation, however, are unknown. Thus, the goal of this study was to determine the possible mechanism(s) through which permethrin reduced insulin-stimulated AKT phosphorylation in C2C12 myotubes. Permethrin treatment, at 10 μM, decreased insulin-stimulated membrane glucose transporter type 4 (GLUT4) and AKT phosphorylation, and increased insulin receptor substrate 1 (IRS1) Ser307 phosphorylation in the presence of insulin. The inactivation of AKT by permethrin was independent of AMPKα. ERK inactivation by U0126, however, restored insulin-stimulated AKT phosphorylation, which was decreased by permethrin treatment. These results suggest that permethrin decreased insulin-stimulated AKT phosphorylation via ERK activation, but not by AMPKα inactivation.
先前有报道称，10 μM氯菊酯（顺式异构体占38.7%，反式异构体占59.4%）这种广泛用于农业和家用产品害虫防治的拟除虫菊酯类杀虫剂，会降低C2C12小鼠肌管中胰岛素刺激的葡萄糖摄取以及蛋白激酶B（p-AKT）的磷酸化水平。然而，氯菊酯降低胰岛素刺激的AKT磷酸化的潜在机制尚不清楚。因此，本研究的目的是确定氯菊酯降低C2C12肌管中胰岛素刺激的AKT磷酸化的可能机制。在存在胰岛素的情况下，用10 μM氯菊酯处理会降低胰岛素刺激的4型膜葡萄糖转运蛋白（GLUT4）和AKT磷酸化水平，并增加胰岛素受体底物1（IRS1）Ser307的磷酸化水平。氯菊酯对AKT的失活作用与AMPKα无关。然而，用U0126抑制ERK可恢复胰岛素刺激的AKT磷酸化水平，而该水平因氯菊酯处理而降低。这些结果表明，氯菊酯通过激活ERK而非使AMPKα失活来降低胰岛素刺激的AKT磷酸化水平。
