Abstract
Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance (IR) and has attracted worldwide attention due to its high prevalence. As a typical persistent organic pollutant, decabromodiphenyl ether (BDE-209) has been detected in food and human samples, and the concentration trends increase year by year. In addition, it has been proved to have the potential to increase the risk of IR, but it is rarely reported whether it could aggravate IR in T2DM. Therefore, in this study, the IR-BRL (buffalo rat liver cells with IR) model was applied to study the metabolism toxicity and susceptibility of BDE-209. Results showed that BDE-209 could inhibit glucose absorption and increase the levels of serum total cholesterol (TC) and triglyceride (TG), ultimately leading to the disorder of glucolipid metabolism in IR-BRL cells. Besides, it also could cause cell damage by increasing the levels of aspartate transaminase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) in cells. Moreover, its potential mechanisms were to: (1) affect the transport of glucose, synthesis of glycogen and fatty acid via IRS-1/GLUT4 and IRS-1/PI3K/AKT/GSK-3β pathways; (2) impact the proliferation and differentiation by regulating the expression of Mek1/2, Erk1/2, and mTOR proteins and genes. Furthermore, susceptibility analysis showed that there was a significant synergism interaction between IR and BDE-209, which suggested that IR-BRL cells were more susceptible to the metabolism toxicity induced by BDE-209.
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The datasets generated or analyzed during this study are available from the corresponding author.
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This work was supported by the State Key Laboratory of Environmental Chemistry and Ecotoxicology Open Fund [KF 2020–11], the Natural Science Foundation of Jiangsu province [BK20160497], the Natural Science Research of Jiangsu Higher Education Institutions of China [16KJB610005], the Senior Talent Foundation of Jiangsu University [15JDG031], and the Priority Academic Program Development of Jiangsu Higher Education Institutions and Collaborative Innovation Center for Water Treatment Technology and Materials.
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Conceptualization: Guanghua Mao; methodology: Guanghua Mao; data curation: Guanghua Mao, Junjie Tang, Taotao Liao, Xiaoxiang Shi, and FangYuan Dong; formal analysis: Guanghua Mao and Junjie Tang; writing—original draft: Guanghua Mao, Junjie Tang, and Taotao Liao; writing—review and editing: Guanghua Mao; funding acquisition: Guanghua Mao; Project administration: Guanghua Mao; visualization: Guanghua Mao and Junjie Tang; investigation: Junjie Tang and Taotao Liao; software: Xiaoxiang Shi, Weiwei Feng, and Yao Chen; validation: FangYuan Dong, Ting Zhao, and Liuqing Yang; project administration: Xiangyang Wu; supervision: Xiangyang Wu and Liuqing Yang.
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Mao, G., Tang, J., Liao, T. et al. Metabolism toxicity and susceptibility of decabromodiphenyl ether (BDE-209) exposure on BRL cells with insulin resistance. Environ Sci Pollut Res 29, 91306–91324 (2022). https://doi.org/10.1007/s11356-022-21980-7
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DOI: https://doi.org/10.1007/s11356-022-21980-7