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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.

Author information

1
Environmental Technology Research Institute, Seoul National University of Science and Technology, Republic of Korea.
2
Department of Environmental Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea. Electronic address: ktkim@seoultech.ac.kr.
3
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: rhyudy@mokpo.ac.kr.

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

PMID:
31923579
DOI:
10.1016/j.tiv.2020.104767

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