title: Mechanism of BDE209-induced impaired glucose homeostasis based on gene microarray analysis of adult rat liver.
abstract: Several persistent organic pollutants are reported to be potentially associated with the risk of human diabetes that has become rapidly epidemic in China currently. 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE209) is commercially most important both in the production and in the use of polybrominated diphenyl ethers (PBDEs). It might bioaccumulate in wildlife and human and is the only PBDEs mixture still used today. In the present study, male adult rats treated with BDE209 (0, 0.05, 1, and 20 mg/kg) for 8 weeks were used to explore the effects of BDE209 on glucose homeostasis and possible mechanisms; 0.05 mg/kg of BDE209 induced dose-related hyperglycemia. Then, we performed the full-genome gene expression microarrays, gene ontology analysis, and pathway analysis in this group and control. BDE209 induced 1,257 liver gene transcript changes, and 18 canonical pathways were significantly enriched. Four of them were involved in immune diseases, including autoimmune thyroid disease, graft-versus-host disease, allograft rejection, and type I diabetes mellitus (T1MD), which was confirmed by the decrease in serum insulin. Subsequently, gene act network and gene co-expression network found that some MHC molecules and TNF-α were involved in T1DM pathway, which was then confirmed by the increase in serum TNF-α. Additionally, reduced glutathione and superoxide dismutase in plasma indicated that oxidative damage might partly contribute to BDE209-induced hyperglycemia. The results of this study provide some new experimental evidence that the exposure to high levels of BDE209 may contribute to the onset of diabetes in human populations. Further work needs to be done to confirm this link.
authors: Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 818 East Tiangyuan Rd., Nanjing, 211166, China.
authors: Zhan
authors: Z
authors: Zhang
authors: Zhen-Zhen
authors: ZZ
authors: Sun
authors: Xue
authors: X
authors: Xiao
authors: Shixin
authors: S
authors: Zhou
authors: Xi-Chen
authors: XC
authors: Wang
authors: Jun
authors: J
authors: Gu
authors: Liang-Lin
authors: LL
authors: Qiu
authors: Xu-Hui
authors: XH
authors: Zhang
authors: Qiujin
authors: Q
authors: Xu
authors: Binghui
authors: B
authors: Zhen
authors: Xinru
authors: X
authors: Wang
authors: Shou-Lin
authors: SL
authors: Wang
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects; D006943:Hyperglycemia / Q000139:chemically induced; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D046228:Microarray Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D055768:Halogenated Diphenyl Ethers; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose; C010902:decabromobiphenyl ether