Low-concentration exposure to organochlorine pesticides (OCPs) in L6 myotubes and RIN-m5F pancreatic beta cells induces disorders of glucose metabolism

Toxicol In Vitro. 2020 Jun;65:104767. doi: 10.1016/j.tiv.2020.104767. Epub 2020 Jan 7.

Abstract

We selected five substances among the organochlorine pesticides (OCPs), chlordane, heptachlor, p,p'-DDT, β-HCH, and hexachlorobenzene, and investigated whether low-concentration exposure to the OCP compounds affected glucose metabolism. The exposure of L6 myotubes to the OCP compounds (1 or 5 μM) for 24 and 48 h significantly inhibited glucose uptake with an excessive production of intracellular reactive oxygen species (ROS) and peroxynitrite anions (ONOO-) compared to control cells. In contrast, the production of nitric oxide was highly reduced by exposure to the OCP compounds. The protein expression of glucose transporter 4 (GLUT4) in the L6 myotubes was significantly suppressed by exposure to the OCP compounds. In addition, exposure to the OCP compounds for 1 h in RIN-m5F pancreatic beta cells remarkably suppressed insulin secretion but the ability to secrete insulin recovered to control levels after 24 h exposure to the OCP compounds. The abundant ROS generated by 1 h exposure to OCP compounds was inversely related to insulin secretion in RIN-m5F pancreatic beta cells. Therefore, these results suggest that low-concenration exposure of skeletal muscle and pancreatic beta cells to OCP compounds may affect insulin secretion and insulin-dependent glucose uptake through extreme oxidative stress and inactivation of the glucose transport protein.

Keywords: Diabetes; Glucose uptake; Insulin secretion; Myotubes; Organochlorine pesticides; Pancreatic beta cells.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Glucose / metabolism
  • Glucose Transporter Type 4 / antagonists & inhibitors
  • Glucose Transporter Type 4 / metabolism
  • Hydrocarbons, Chlorinated / toxicity*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism
  • Nitric Oxide / metabolism
  • Peroxynitrous Acid / metabolism
  • Pesticides / toxicity*
  • Rats

Substances

  • Glucose Transporter Type 4
  • Hydrocarbons, Chlorinated
  • Pesticides
  • Slc2a4 protein, rat
  • Peroxynitrous Acid
  • Nitric Oxide
  • Glucose