title: Chronic Exposure to Aroclor 1254 Disrupts Glucose Homeostasis in Male Mice via Inhibition of the Insulin Receptor Signal Pathway.
abstract: Epidemiological studies demonstrate that polychlorinated biphenyls (PCBs) induce diabetes and insulin resistance. However, the development of diabetes caused by PCBs and its underlying mechanisms are still unclear. In the present study, male C57BL/6 mice were orally administered with Aroclor 1254 (0.5, 5, 50, and 500 μg/kg) once every 3 days for 60 days. The body weight and the fasting blood glucose levels were significantly elevated; the levels of serum insulin, resistin, tumor necrosis factor α (TNFα), and interleukin-6 (IL-6) increased, while glucagon levels decreased in the animals treated with Aroclor 1254. Pancreatic β-cell mass significantly increased, while α-cell mass was reduced. Aroclor 1254 inhibited the expression of the insulin receptor signaling cascade, including insulin receptor, insulin receptor substrate, phosphatidylinositol 3-kinase-Akt, and protein kinase B and glucose transporter 4, both in the skeletal muscle and the liver. The results suggested that chronic exposure to Aroclor 1254 disrupted glucose homeostasis and induced hyperinsulinemia. The significant elevation of serum resistin, TNFα and IL-6 indicated that obesity caused by Aroclor 1254 is associated with insulin resistance. The elevation of blood glucose levels could have been mainly as a result of insulin receptor signals pathway suppression in skeletal muscle and liver, and a decrease in pancreatic α-cells, accompanied by a reduction of serum glucagon levels, may play an important role in the development of type 2 diabetes.
authors.affiliation: †State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361006, P.R. China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: †State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361006, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wu
authors.affiliation: §Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, Xiamen University, Xiamen 361006, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
authors.affiliation: †State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361006, P.R. China.
authors.forename: Zhizhun
authors.initials: Z
authors.lastname: Guo
authors.affiliation: †State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361006, P.R. China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: †State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361006, P.R. China.|§Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, Xiamen University, Xiamen 361006, P.R. China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: †State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361006, P.R. China.|‡State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361006, P.R. China.
authors.forename: Chonggang
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000150:complications; D006706:Homeostasis / Q000187:drug effects*; D006943:Hyperglycemia / Q000150:complications; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls; D011972:Receptor, Insulin; D005947:Glucose