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

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.