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Article

Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels

  • Authors:
    • Yi‑Min Chen
    • Jin‑Fang Zhao
    • Yong‑Lin Liu
    • Jie Chen
    • Rong‑Lin Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China, Department of Endocrinology, The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Intensive Care Unit, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
  • Pages: 739-746
    |
    Published online on: July 13, 2015
       https://doi.org/10.3892/ijmm.2015.2282
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Abstract

The present study aimed to investigate the effects of ethanol treatment on the induction of intracellular calcium ([Ca2+]i) levels and the inhibition of the activation of the insulin signaling pathway in human hepatocytes. L‑02 cells were treated with various concentrations of ethanol for different periods of time. Cell viability and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) leakage in the culture supernatant were evaluated. Changes in [Ca2+]i levels were detected by flow cytometry and confocal microscopy. Total RNA and protein were extracted to examine the mRNA and protein levels of insulin receptor substrate (IRS)1, IRS2, phosphatidylinositol 3‑kinase (PI3K) and glucose transporter 2 (GLUT2) by reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis, respectively. Furthermore, insulin was added to the ethanol‑treated L‑02 cells, and the phosphorylation levels of PI3K and protein kinase B (PKB) were determined by western blot analysis before and after Ca2+ blockage. No significant changes were observed in cell viability, [Ca2+]i levels and in the expression and phosphorylation levels of insulin signal transduction molecules when the L‑02 cells were treated with 0.5 or 1% ethanol. However, treatment with 2 or 4% ethanol resulted in a significant decrease in cell viability and in the mRNA levels of IRS1, IRS2, PI3K (p85α) and GLUT2, as well as in an increase in ALT/AST leakage and in the [Ca2+]i levels (P<0.05). The expression and phosphorylation levels of PI3K (p85α) and PKB were also inhibited by treatment with 2 or 4% ethanol. These cytological effects induced by ethanol treatment were partially reversed by Ca2+ blockage. These results suggest that ethanol treatment inhibits the activation of the insulin signal transduction pathway in a dose‑, time‑ and Ca2+‑dependent manner. The inhibition of IRS1/2, PI3K (p85α), PKB and GLUT2 expression and of PI3K (p85α) and PKB phosphorylation by the high concentrations of ethanol may be the core molecular mechanism of ethanol-induced insulin resistance, and may be related to the induction of [Ca2+]i levels.
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1 

Wannamethee SG, Shaper AG, Perry IJ and Alberti KG: Alcohol consumption and the incidence of type II diabetes. J Epidemiol Community Health. 56:542–548. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Pietraszek A, Gregersen S and Hermansen K: Alcohol and type 2 diabetes. A review. Nutr Metab Cardiovasc Dis. 20:366–375. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Cullmann M, Hilding A and Östenson CG: Alcohol consumption and risk of pre-diabetes and type 2 diabetes development in a Swedish population. Diabet Med. 29:441–452. 2012. View Article : Google Scholar

4 

Fan AZ, Russell M, Naimi T, Li Y, Liao Y, Jiles R and Mokdad AH: Patterns of alcohol consumption and the metabolic syndrome. J Clin Endocrinol Metab. 93:3833–3838. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Petersen KF and Shulman GI: Etiology of insulin resistance. Am J Med. 119(Suppl 1): S10–S16. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Ismail-Beigi F: Pathogenesis and glycemic management of type 2 diabetes mellitus: a physiological approach. Arch Iran Med. 15:239–246. 2012.PubMed/NCBI

7 

Bechmann LP, Hannivoort RA, Gerken G, Hotamisligil GS, Trauner M and Canbay A: The interaction of hepatic lipid and glucose metabolism in liver diseases. J Hepatol. 56:952–964. 2012. View Article : Google Scholar

8 

Saltiel AR and Kahn CR: Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 414:799–806. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Liu H, Jia X, Luo Z, Guan H, Jiang H, Li X and Yan M: Inhibition of store-operated Ca2+ channels prevent ethanol-induced intracellular Ca2+ increase and cell injury in a human hepatoma cell line. Toxicol Lett. 208:254–261. 2012. View Article : Google Scholar

10 

Vagts AJ, He DY, Yaka R and Ron D: Cellular adaptation to chronic ethanol results in altered compartmentalization and function of the scaffolding protein RACK1. Alcohol Clin Exp Res. 27:1599–1605. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Shih CL, Chi SI, Chiu TH, Sun GY and Lin TN: Ethanol effects on nitric oxide production in cerebral pial cultures. Alcohol Clin Exp Res. 25:612–618. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Kim E, Seok HH, Lee SY, Lee DR, Moon J, Yoon TK, Lee WS and Lee KA: Correlation between expression of glucose transporters in granulosa cells and oocyte quality in women with polycystic ovary syndrome. Endocrinol Metab (Seoul). 29:40–47. 2014. View Article : Google Scholar

13 

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

14 

Thiele TE: Insulin resistance from binge drinking: It's all in your head. Sci Transl Med. 5:170fs32013. View Article : Google Scholar : PubMed/NCBI

15 

Tang YL, Xiang XJ, Wang XY, Cubells JF, Babor TF and Hao W: Alcohol and alcohol-related harm in China: policy changes needed. Bull World Health Organ. 91:270–276. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Carlsson S, Hammar N, Grill V and Kaprio J: Alcohol consumption and the incidence of type 2 diabetes: a 20-year follow-up of the Finnish twin cohort study. Diabetes Care. 26:2785–2790. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Lee K: Gender-specific relationships between alcohol drinking patterns and metabolic syndrome: the Korea National Health and Nutrition Examination Survey 2008. Public Health Nutr. 15:1917–1924. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Onishi Y, Honda M, Ogihara T, Sakoda H, Anai M, Fujishiro M, Ono H, Shojima N, Fukushima Y, Inukai K, et al: Ethanol feeding induces insulin resistance with enhanced PI 3-kinase activation. Biochem Biophys Res Commun. 303:788–794. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Wilkes JJ, DeForrest LL and Nagy LE: Chronic ethanol feeding in a high-fat diet decreases insulin-stimulated glucose transport in rat adipocytes. Am J Physiol. 271:E477–E484. 1996.PubMed/NCBI

20 

Xu D, Dhillon AS, Davey CG, Fournier PA and Palmer TN: Alcohol and glucose metabolism in skeletal muscles in the rat. Addict Biol. 1:71–83. 1996. View Article : Google Scholar : PubMed/NCBI

21 

Guo S: Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms. J Endocrinol. 220:T1–T23. 2014. View Article : Google Scholar

22 

White MF: Insulin signaling in health and disease. Science. 302:1710–1711. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Kadowaki T: Insights into insulin resistance and type 2 diabetes from knockout mouse models. J Clin Invest. 106:459–465. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, et al: Disruption of IRS-2 causes type 2 diabetes in mice. Nature. 391:900–904. 1998. View Article : Google Scholar : PubMed/NCBI

25 

Kido Y, Burks DJ, Withers D, Bruning JC, Kahn CR, White MF and Accili D: Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J Clin Invest. 105:199–205. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Benito M: Tissue specificity on insulin action and resistance: past to recent mechanisms. Acta Physiol (Oxf). 201:297–312. 2011. View Article : Google Scholar

27 

Pagliassotti MJ, Kang J, Thresher JS, Sung CK and Bizeau ME: Elevated basal PI 3-kinase activity and reduced insulin signaling in sucrose-induced hepatic insulin resistance. Am J Physiol Endocrinol Metab. 282:E170–E176. 2002.

28 

Nevado C, Valverde AM and Benito M: Role of insulin receptor in the regulation of glucose uptake in neonatal hepatocytes. Endocrinology. 147:3709–3718. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Karim S, Adams DH and Lalor PF: Hepatic expression and cellular distribution of the glucose transporter family. World J Gastroenterol. 18:6771–6781. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Cui RB, Kan BT, Sun XM, Luo Z, Guo R, Guo XL and Yan M: Role of store-operated Ca2+ channels in primary hepatocytes under conditions of calcium overload and ethanol-induced injury. Zhonghua Gan Zang Bing Za Zhi. 21:860–864. 2013.In Chinese. PubMed/NCBI

31 

Caro AA and Cederbaum AI: Role of calcium and calcium-activated proteases in CYP2E1-dependent toxicity in HEPG2 cells. J Biol Chem. 277:104–113. 2002. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Chen YM, Zhao JF, Liu YL, Chen J and Jiang RL: Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels. Int J Mol Med 36: 739-746, 2015.
APA
Chen, Y., Zhao, J., Liu, Y., Chen, J., & Jiang, R. (2015). Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels. International Journal of Molecular Medicine, 36, 739-746. https://doi.org/10.3892/ijmm.2015.2282
MLA
Chen, Y., Zhao, J., Liu, Y., Chen, J., Jiang, R."Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels". International Journal of Molecular Medicine 36.3 (2015): 739-746.
Chicago
Chen, Y., Zhao, J., Liu, Y., Chen, J., Jiang, R."Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels". International Journal of Molecular Medicine 36, no. 3 (2015): 739-746. https://doi.org/10.3892/ijmm.2015.2282
Copy and paste a formatted citation
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Spandidos Publications style
Chen YM, Zhao JF, Liu YL, Chen J and Jiang RL: Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels. Int J Mol Med 36: 739-746, 2015.
APA
Chen, Y., Zhao, J., Liu, Y., Chen, J., & Jiang, R. (2015). Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels. International Journal of Molecular Medicine, 36, 739-746. https://doi.org/10.3892/ijmm.2015.2282
MLA
Chen, Y., Zhao, J., Liu, Y., Chen, J., Jiang, R."Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels". International Journal of Molecular Medicine 36.3 (2015): 739-746.
Chicago
Chen, Y., Zhao, J., Liu, Y., Chen, J., Jiang, R."Chronic ethanol treatment of human hepatocytes inhibits the activation of the insulin signaling pathway by increasing cytosolic free calcium levels". International Journal of Molecular Medicine 36, no. 3 (2015): 739-746. https://doi.org/10.3892/ijmm.2015.2282
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