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Toxicol In Vitro. 2020 Jan 7;65:104767. doi: 10.1016/j.tiv.2020.104767. [Epub ahead of print]

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

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Environmental Technology Research Institute, Seoul National University of Science and Technology, Republic of Korea.
Department of Environmental Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea. Electronic address:
Department of Oriental Medicine Resources, Institute of Korean Herbal Medicine Industry, College of Natural Sciences, Mokpo National University, 1666, Youngsan-ro, Muan-gun, Jeonnam 58554, Republic of Korea. Electronic address:


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.


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


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