Adverse impact of carbon tetrachloride on metabolic function in mice.

Carbon tetrachloride (CCl ), a potent hepatotoxin, is linked to the histopathological outcomes of inflammatory or oxidative stress, and cell death. However, further study of additional dysmetabolism induced by CCl toxicant has not yet been investigated. In current study, chronical and acute exposures of CCl in mice were used to unmask the biological molecular mechanism responsible for insulin-dependent metabolic disorder. In experimental methods, a number of biochemical assays were used in assessment of biological impacts on insulin-produced pancreas and insulin-responsive hepatocyte after long- and short-term exposures of CCl toxicant, respectively. As a result, data from oral glucose tolerance test showed that CCl exposures induced glucose tolerance and disrupted blood insulin and glucagon levels time-dependently. Meanwhile, biochemical and histocytological analyses further indicated that CCl exposures significantly resulted in liver cell damage, induced abnormal changes of hepatic and skeletal glycogen synthesis. In addition, acute CCl -exposed mice showed reduced functional proteins of glucose transporter 2 (GLUT2), insulin receptor β, insulin receptor substrate 1, glycogen synthase kinase 3β (GSK3β), p-AKT associated with AKT signaling pathway in liver cells, whereas acute CCl exposure downregulated the endogenous expressions of the insulin and glucagon hormonal proteins in the pancreas. Taken together, the current findings highlight that CCl impaired insulin-dependent glucose homeostasis through modulating hepatocellular AKT signaling pathway in acute CCl exposure and GLUT2/GSK3β pathway in chronic CCl -exposed liver cells.