PTEN in propofol‑induced insulin resistance in mouse primary hepatocytes

Zhou,Long; Wang,Lilin; Hu,Xuhuai; Li,Yuantao

doi:10.3892/etm.2018.6815

PTEN in propofol‑induced insulin resistance in mouse primary hepatocytes

Authors:
- Long Zhou
- Lilin Wang
- Xuhuai Hu
- Yuantao Li
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Affiliations: Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong 518000, P.R. China, Shenzhen Blood Center, Shenzhen, Guangdong 518000, P.R. China, Shenzhen Health Development Research Center, Shenzhen, Guangdong 518000, P.R. China
Published online on: October 1, 2018 https://doi.org/10.3892/etm.2018.6815
Pages: 4831-4835

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Abstract

Propofol is the most common intravenous anesthetic agent used in clinical practice. Propofol can induce insulin resistance in mouse primary hepatocytes, however the molecular mechanism through which propofol acts remains largely unknown. Based on previous studies, it was hypothesized that phosphatase and tensin homolog (PTEN) is involved in propofol‑mediated insulin resistance. The aim of the present study was to investigate the biological function of PTEN and its molecular mechanism in propofol‑induced insulin resistance in mouse primary hepatocytes. Mouse primary hepatocytes were treated with propofol and transfected with small interfering RNA (siRNA)‑996 to silence the endogenous expression of PTEN. The current study assessed the effects of propofol and PTEN knockdown on the expression of PTEN and several key enzymes of the phosphoinositide 3‑kinase/protein kinase B/glycogen synthase kinase‑3β signaling pathway, as well as the glycogen content in mouse primary hepatocytes. Treatment with propofol significantly increased protein and mRNA PTEN expression in mouse primary hepatocytes. In addition, knockdown of PTEN reversed propofol‑induced insulin resistance in mouse primary hepatocytes. The present study indicated that PTEN serves a role in the physiological process of propofol‑induced insulin resistance in mouse primary hepatocytes, and PTEN inhibition may be a potential target for therapeutic intervention against propofol‑induced adverse effects.

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1	Miller RD: Miller's anesthesia. Eighth. Philadelphia: Elsevier Saunders; pp. 822–831. 2015
2	Vanhorebeek I, Gunst J and Van den Berghe G: Critical care management of stress-induced hyperglycemia. Curr Diab Rep. 18:172018. View Article : Google Scholar : PubMed/NCBI
3	Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H and Bouillon R: Intensive insulin therapy in the medical ICU. N Engl J Med. 354:449–461. 2006. View Article : Google Scholar : PubMed/NCBI
4	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
5	Zhou L, Wang L, Yang B, Zeng J, Zhang Q, Lei H and Xu S: Protective effect of pretreatment with propofol against tumor necrosis factor-α-induced hepatic insulin resistance. Exp Ther Med. 10:289–294. 2015. View Article : Google Scholar : PubMed/NCBI
6	Milne SE, Troy A, Irwin MG and Kenny GN: Relationship between bispectral index, auditory evoked potential index and effect-site EC50 for propofol at two clinical end-points. Br J Anaesth. 90:127–131. 2003. View Article : Google Scholar : PubMed/NCBI
7	Smith C, McEwan AI, Jhaveri R, Wilkinson M, Goodman D, Smith LR, Canada AT and Glass PS: 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
8	Hsing CH, Chen YH, Chen CL, Huang WC, Lin MC, Tseng PC, Wang CY, Tsai CC, Choi PC and Lin CF: Anesthetic propofol causes glycogen synthase kinase-3β-regulated lysosomal/mitochondrial apoptosis in macrophages. Anesthesiology. 116:868–881. 2012. View Article : Google Scholar : PubMed/NCBI
9	Driessen GJ, IJspeert H, Wentink M, Yntema HG, van Hagen PM, van Strien A, Bucciol G, Cogulu O, Trip M, Nillesen W, et al: Increased PI3K/Akt activity and deregulated humoral immune response in human PTEN deficiency. J Allergy Clin Immunol. 138:1744–1747.e5. 2016. View Article : Google Scholar : PubMed/NCBI
10	Yue S, Li J, Lee SY, Lee HJ, Shao T, Song B, Cheng L, Masterson TA, Liu X, Ratliff TL and Cheng JX: Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 19:393–406. 2014. View Article : Google Scholar : PubMed/NCBI
11	Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW and Holland EC: PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell. 4:226–235. 2009. View Article : Google Scholar : PubMed/NCBI
12	Wishart MJ and Dixon JE: PTEN and myotubularin phosphatases: From 3-phosphoinositide dephosphorylation to disease. Trends Cell Biol. 12:579–585. 2002. View Article : Google Scholar : PubMed/NCBI
13	Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K and Tuschl T: Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 411:494–498. 2001. View Article : Google Scholar : PubMed/NCBI
14	Shi XP, Zong AN, Tao J and Wang LZ: Study of instructive notions with respect to caring for laboratory animals. J China Med Univ. 36:4932007.
15	Seglen PO: Preparation of isolated rat liver cells. Methods Cell Biol. 13:29–83. 1976. View Article : Google Scholar : PubMed/NCBI
16	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
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
18	Lebovitz HE: Insulin resistance: Definition and consequences. Exp Clin Endocrinol Diabetes. 109 Suppl 2:S135–S148. 2001. View Article : Google Scholar : PubMed/NCBI
19	Reaven GM: Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 37:1595–1607. 1988. View Article : Google Scholar : PubMed/NCBI
20	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
21	van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P and Bouillon R: Intensive insulin therapy in critically ill patients. N Engl J Med. 345:1359–1367. 2001. View Article : Google Scholar : PubMed/NCBI
22	Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, et al: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 275:1943–1947. 1997. View Article : Google Scholar : PubMed/NCBI
23	Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, et al: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 15:356–362. 1997. View Article : Google Scholar : PubMed/NCBI
24	Li DM and Sun H: TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res. 57:2124–2129. 1997.PubMed/NCBI
25	Chu EC and Tarnawski AS: PTEN regulatory functions in tumor suppression and cell biology. Med Sci Monit. 10:RA235–RA241. 2004.PubMed/NCBI
26	Sha SH, Chen FQ and Schacht J: PTEN attenuates PIP3/Akt signaling in the cochlea of the aging CBA/J mouse. Hear Res. 264:86–92. 2010. View Article : Google Scholar : PubMed/NCBI
27	Leslie NR, Bennett D, Lindsay YE, Stewart H, Gray A and Downes CP: Redox regulation of PI 3-kinase signalling via inactivation of PTEN. EMBO J. 22:5501–5510. 2003. View Article : Google Scholar : PubMed/NCBI