Adverse impact of carbon tetrachloride on metabolic function in mice

Carbon tetrachloride (CCl₄ ), 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 ₄ toxicant has not yet been investigated. In current study, chronical and acute exposures of CCl ₄ 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 ₄ toxicant, respectively. As a result, data from oral glucose tolerance test showed that CCl ₄ exposures induced glucose tolerance and disrupted blood insulin and glucagon levels time-dependently. Meanwhile, biochemical and histocytological analyses further indicated that CCl ₄ exposures significantly resulted in liver cell damage, induced abnormal changes of hepatic and skeletal glycogen synthesis. In addition, acute CCl ₄ -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 ^Ser473 associated with AKT signaling pathway in liver cells, whereas acute CCl ₄ exposure downregulated the endogenous expressions of the insulin and glucagon hormonal proteins in the pancreas. Taken together, the current findings highlight that CCl ₄ impaired insulin-dependent glucose homeostasis through modulating hepatocellular AKT signaling pathway in acute CCl ₄ exposure and GLUT2/GSK3β pathway in chronic CCl ₄ -exposed liver cells.