Chronic Exposure to Aroclor 1254 Disrupts Glucose Homeostasis in Male Mice via Inhibition of the Insulin Receptor Signal Pathway

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 mu g/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 alpha (TNF alpha), and interleukin-6 (IL-6) increased, while glucagon levels decreased in the animals treated with Arodor 1254. Pancreatic beta-cell mass significantly increased, while alpha-cell mass was reduced. Arodor 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 Arodor 1254 disrupted glucose homeostasis and induced hyperinsulinemia. The significant elevation of serum resistin, TNF alpha 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 alpha-cells, accompanied by a reduction of serum glucagon levels, may play an important role in the development of type 2 diabetes.