Adverse impact of carbon tetrachloride on metabolic function in mice. Issue 7 (18th February 2019)

• Record Type: Journal Article
• Authors: Liang, Xiaoliu; Wu, Ka; Liu, Meizhen; Yang, Bin
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 7(2019)
• Page Start: 11973
• Page End: 11980
• Publication Date: 2019-02-18
• Subjects: carbon tetrachloride -- dysmetabolism -- liver -- molecular pathway -- pancreas; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28481
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: 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. Abstract : The current findings highlight that CCl4 impaired insulin‐dependent glucose metabolism via negatively regulating AKT signaling pathway in the liver.