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

Food Chem Toxicol. 2017 Nov;109(Pt 1):95-101. doi: 10.1016/j.fct.2017.08.046. Epub 2017 Sep 1.

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.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Glucose Transporter Type 4 / metabolism
  • Insecticides / pharmacology*
  • Insulin / metabolism*
  • Mice
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Fibers, Skeletal / metabolism
  • Permethrin / pharmacology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects

Substances

  • Glucose Transporter Type 4
  • Insecticides
  • Insulin
  • Permethrin
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 3
  • AMP-Activated Protein Kinases