Metabolism toxicity and susceptibility of decabromodiphenyl ether (BDE-209) exposure on BRL cells with insulin resistance

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 to 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 the glucose absorption and increase the levels of TC and TG, ultimately lead to the disorder of glucolipid metabolism in IR-BRL cells.Besides, it also could cause cell damage by increasing the levels of AST, ALT and 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 signi cant synergism interaction between IR and BDE-209, which suggested that IR-BRL cells were more susceptible to the metabolism toxicity induced by BDE-209.

Toxic Effects and Mechanisms of Polybrominated Diphenyl Ethers

“…The reduced GSH and SOD implied that oxidative damage may contribute to PBDE-209-induced hyperglycemia and the onset of diabetes [70]. PBDE-209 has been reported to hinder glucose absorption, increase the levels of total cholesterol (TC), TG, aspartate transaminase (AST), alanine aminotransferase (ALT), and MDA through insulin receptor substrate-1 (IRS-1)/GLUT4 and IRS-1/PI3K/AKT/Glycogen synthase kinase 3β (GSK-3β) pathways, eventually interfering with glucolipid metabolism in buffalo rat liver cells with insulin resistance (IR-BRL) [71]. The mechanisms are shown in Figure 4.…”