Protective effect of pretreatment with propofol against tumor necrosis factor-α-induced hepatic insulin resistance

Zhou,Long; Wang,Lilin; Yang,Baocheng; Zeng,Jinfeng; Zhang,Qingguo; Lei,Hongyi; Xu,Shiyuan

doi:10.3892/etm.2015.2496

Protective effect of pretreatment with propofol against tumor necrosis factor-α-induced hepatic insulin resistance

Authors:
- Long Zhou
- Lilin Wang
- Baocheng Yang
- Jinfeng Zeng
- Qingguo Zhang
- Hongyi Lei
- Shiyuan Xu
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Affiliations: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Shenzhen Blood Center, Shenzhen, Guangdong 518035, P.R. China
Published online on: May 15, 2015 https://doi.org/10.3892/etm.2015.2496
Pages: 289-294

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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.

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1	Fahy BG, Sheehy AM and Coursin DB: Glucose control in the intensive care unit. Crit Care Med. 37:1769–1776. 2009. View Article : Google Scholar : PubMed/NCBI
2	Gauglitz GG, Herndon DN and Jeschke MG: Insulin resistance postburn: Underlying mechanisms and current therapeutic strategies. J Burn Care Res. 29:683–694. 2008. View Article : Google Scholar : PubMed/NCBI
3	Lipshutz AK and Gropper MA: Perioperative glycemic control: An evidence-based review. Anesthesiology. 110:408–421. 2009.PubMed/NCBI
4	Coursin DB, Connery LE and Ketzler JT: Perioperative diabetic and hyperglycemic management issues. Crit Care Med. 32:(Suppl). S116–S125. 2004. View Article : Google Scholar : PubMed/NCBI
5	van den Berghe G, Wouters P, Weekers F, et al: Intensive insulin therapy in critically ill patients. N Engl J Med. 345:1359–1367. 2001. View Article : Google Scholar : PubMed/NCBI
6	Krinsley JS: Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc. 78:1471–1478. 2003. View Article : Google Scholar : PubMed/NCBI
7	Laird AM, Miller PR, Kilgo PD, Meredith JW and Chang MC: Relationship of early hyperglycemia to mortality in trauma patients. J Trauma. 56:1058–1062. 2004. View Article : Google Scholar : PubMed/NCBI
8	Deedwania P, Kosiborod M, Barrett E, Ceriello A, Isley W, Mazzone T and Raskin P: American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity, and Metabolism: Hyperglycemia and acute coronary syndrome: A scientific statement from the American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 117:1610–1619. 2008. View Article : Google Scholar : PubMed/NCBI
9	Yasuda Y, Fukushima Y, Kaneki M and Martyn JA: Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats. Biochem Biophys Res Commun. 431:81–85. 2013. View Article : Google Scholar : PubMed/NCBI
10	Felig P and Wahren J: Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J Clin Invest. 50:1702–1711. 1971. View Article : Google Scholar : PubMed/NCBI
11	Pehmøller C, Brandt N, Birk JB, et al: Exercise alleviates lipid-induced insulin resistance in human skeletal muscle-signaling interaction at the level of TBC1 domain family member 4. Diabetes. 61:2743–2752. 2012. View Article : Google Scholar : PubMed/NCBI
12	Schenk S and Horowitz JF: Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. J Clin Invest. 117:1690–1698. 2007. View Article : Google Scholar : PubMed/NCBI
13	Boden G, Lebed B, Schatz M, Homko C and Lemieux S: Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects. Diabetes. 50:1612–1617. 2001. View Article : Google Scholar : PubMed/NCBI
14	Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J and Feve B: Recent advances in the relationship between obesity, inflammation and insulin resistance. Eur Cytokine Netw. 17:4–12. 2006.PubMed/NCBI
15	Xu J, Kim HT, Ma Y, Zhao L, Zhai L, Kokorina N, Wang P and Messina JL: Trauma and hemorrhage-induced acute hepatic insulin resistance: Dominant role of tumor necrosis factor-α. Endocrinology. 149:2369–2382. 2008. View Article : Google Scholar : PubMed/NCBI
16	Plomgaard P, Nielsen AR, Fischer CP, Mortensen OH, Broholm C, Penkowa M, Krogh-Madsen R, Erikstrup C, Lindegaard B, Petersen AM, et al: Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes. Diabetologia. 50:2562–2571. 2007. View Article : Google Scholar : PubMed/NCBI
17	Shi XP, Zong A, Tao J and Wang L: Study of instructive notions with respect to caring for laboratory animals. Zhong Guo Yi Ke Da Xue Xue. 36:493. 2007.(In Chinese).
18	Seglen PO: Preparation of isolated rat liver cells. Methods Cell Biol. 13:29–83. 1976.PubMed/NCBI
19	Casciano DA: Development and utilization of primary hepatocyte culture systems to evaluate metabolism, DNA binding, and DNA repair of xenobiotics. Drug Metab Rev. 32:1–13. 2000. View Article : Google Scholar : PubMed/NCBI
20	Smith C, McEwan AI, Jhaveri R, et al: The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. Anesthesiology. 81:820–828; discussion 26A. 1994. View Article : Google Scholar : PubMed/NCBI
21	Hsing CH, Chen YH, Chen CL, et al: Anesthetic propofol causes glycogen synthase kinase-3β-regulated lysosomal/mitochondrial apoptosis in macrophages. Anesthesiology. 116:868–881. 2012. View Article : Google Scholar : PubMed/NCBI
22	Muniyappa R, Lee S, Chen H and Quon MJ: Current approaches for assessing insulin sensitivity and resistance in vivo: Advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 294:E15–E26. 2008. View Article : Google Scholar : PubMed/NCBI
23	Morino S, Kondo T, Sasaki K, et al: Mild electrical stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling. PLoS One. 3:e40682008. View Article : Google Scholar : PubMed/NCBI
24	Liu P, Cheng H, Roberts TM and Zhao JJ: Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 8:627–644. 2009. View Article : Google Scholar : PubMed/NCBI
25	Hong M, Chen DC, Klein PS and Lee VM: Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. J Biol Chem. 272:25326–25332. 1997. View Article : Google Scholar : PubMed/NCBI
26	Ryves WJ and Harwood AJ: Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem Biophys Res Commun. 280:720–725. 2001. View Article : Google Scholar : PubMed/NCBI
27	Hotamisligil GS: Inflammatory pathways and insulin action. Int J Obes Relat Metab Disord. 27:(Suppl 3). S53–S55. 2003. View Article : Google Scholar : PubMed/NCBI
28	Stephens JM, Lee J and Pilch PF: Tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J Biol Chem. 272:971–976. 1997. View Article : Google Scholar : PubMed/NCBI
29	Baeuerle PA and Baltimore D: NF-kappa B: Ten years after. Cell. 87:13–20. 1996. View Article : Google Scholar : PubMed/NCBI
30	Li Y, Yan H, Zhang Z, Zhang G, Sun Y, Yu P, Wang Y and Xu L: Andrographolide derivative AL-1 improves insulin resistance through down-regulation of NF-κB signalling pathway. Br J Pharmacol. 2015.(Epub ahead of print). View Article : Google Scholar
31	Zhou MS, Liu C, Tian R, Nishiyama A and Raij L: Skeletal muscle insulin resistance in salt-sensitive hypertension: Role of angiotensin II activation of NF-κB. Cardiovasc Diabetol. 14:452015. View Article : Google Scholar : PubMed/NCBI
32	Tak PP and Firestein GS: NF-κB: A key role in inflammatory diseases. J Clin Invest. 107:7–11. 2001. View Article : Google Scholar : PubMed/NCBI
33	Gao Z, Hwang D, Bataille F, Lefevre M, York D, Quon MJ and Ye J: Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J Biol Chem. 277:48115–48121. 2002. View Article : Google Scholar : PubMed/NCBI
34	Du QH, Xu YB, Zhang MY, Yun P and He CY: Propofol induces apoptosis and increases gemcitabine sensitivity in pancreatic cancer cells in vitro by inhibition of nuclear factor-κB activity. World J Gastroenterol. 19:5485–5492. 2013. View Article : Google Scholar : PubMed/NCBI
35	Ye HH, Wu KJ, Fei SJ, Zhang XW, Liu HX, Zhang JL and Zhang YM: Propofol participates in gastric mucosal protection through inhibiting the Toll-like receptor-4/nuclear factor kappa-B signaling pathway. Clin Res Hepatol Gastroenterol. 37:e3–e15. 2013. View Article : Google Scholar : PubMed/NCBI
36	Li Q, Zhang L, Han Y, Jiang Z and Wang Q: Propofol reduces MMPs expression by inhibiting NF-κB activity in human MDA-MB-231 cells. Biomed Pharmacother. 66:52–56. 2012. View Article : Google Scholar : PubMed/NCBI
37	Hsing CH, Lin MC, Choi PC, et al: Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKbeta/NF-κB signaling. PLoS One. 6:e175982011. View Article : Google Scholar : PubMed/NCBI
38	Li H, Tan J, Zou Z, Huang CG and Shi XY: Propofol post-conditioning protects against cardiomyocyte apoptosis in hypoxia/reoxygenation injury by suppressing nuclear factor-kappa B translocation via extracellular signal-regulated kinase mitogen-activated protein kinase pathway. Eur J Anaesthesiol. 28:525–534. 2011. View Article : Google Scholar : PubMed/NCBI