@article {12436, title = {Permethrin decreased insulin-stimulated AKT phosphorylation dependent on extracellular signal-regulated kinase-1 (ERK), but not AMP-activated protein kinase α (AMPKα), in C2C12 myotubes.}, journal = {Food Chem Toxicol}, volume = {109}, year = {2017}, month = {2017 Nov}, pages = {95-101}, abstract = {

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.

}, keywords = {AMP-Activated Protein Kinases, Animals, Glucose Transporter Type 4, Insecticides, Insulin, Mice, Mitogen-Activated Protein Kinase 3, Muscle Fibers, Skeletal, Permethrin, Phosphorylation, Proto-Oncogene Proteins c-akt, Signal Transduction}, issn = {1873-6351}, doi = {10.1016/j.fct.2017.08.046}, author = {Sun, Quancai and Peng, Ye and Qi, Weipeng and Kim, Yoo and Clark, John M and Kim, Daeyoung and Park, Yeonhwa} }