title: Protective effect of pretreatment with propofol against tumor necrosis factor-α-induced hepatic insulin resistance.
abstract: Insulin resistance is common in critically ill patients and seriously affects their prognosis. The anesthetic propofol (2,6-diisopropylphenol) has been shown to cause insulin resistance in rats; however, the specific mechanism underlying this phenomenon remains unknown. Thus, the aim of the present study was to determine the molecular mechanism through which propofol influences insulin resistance in the liver. The current study assessed the effects of propofol on the phosphorylation level of key enzymes involved in the insulin signaling pathway, as well as the glycogen content in primary mouse hepatocytes. Propofol administration was demonstrated to considerably reduce the phosphorylation levels of Akt (Ser473) and glycogen synthase kinase (GSK)-3β (Ser9) in the primary mouse hepatocytes. In addition, propofol was shown to downregulate the phosphoinositide 3-kinase (PI3K)/Akt/GSK-3β signaling pathway and inhibit glycogen synthesis in hepatocytes. Thus, the present results indicated that propofol induced insulin resistance in primary mouse hepatocytes. Notably, pretreatment with propofol in tumor necrosis factor (TNF)-α-induced primary mouse hepatocytes with insulin resistance was demonstrated to alleviate the inhibitory effects of TNF-α on the PI3K/Akt/GSK-3β signaling pathway and glycogen synthesis. These results indicated that propofol exerts a protective effect against insulin resistance in primary mouse hepatocytes induced by TNF-α, indicating that propofol therapy may be clinically feasible to alleviate insulin resistance in critically ill patients.
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China ; Department of Medicine, Shenzhen Family Planning Service Center, Shenzhen, Guangdong 518028, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Shenzhen Blood Center, Shenzhen, Guangdong 518035, P.R. China.
authors.forename: Lilin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shenzhen Blood Center, Shenzhen, Guangdong 518035, P.R. China.
authors.forename: Baocheng
authors.initials: B
authors.lastname: Yang
authors.affiliation: Shenzhen Blood Center, Shenzhen, Guangdong 518035, P.R. China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Xu
keywords: glycogen; glycogen synthase kinase-3β; insulin resistance; mouse primary hepatocytes; propofol; protein kinase B