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Article

Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin

  • Authors:
    • Ou Yang
    • Jinliang Li
    • Haiyan Chen
    • Jie Li
    • Jian Kong
  • View Affiliations / Copyright

    Affiliations: Department of Cadre Ward, First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Cardiology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150001, P.R. China
  • Pages: 2791-2798
    |
    Published online on: July 27, 2016
       https://doi.org/10.3892/mmr.2016.5564
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Abstract

The aim of the present study was to establish an endothelial cell model of endothelium-specific insulin resistance to evaluate the effect of atorvastatin on insulin resistance-associated endothelial dysfunction and to identify the potential pathway responsible for its action. Cultured human umbilical vein endothelial cells (HUVECs) were pretreated with different concentrations of glucose with, or without, 10‑5 M insulin for 24 h, following which the cells were treated with atorvastatin. The tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS‑1), the production of nitric oxide (NO), the activity and phosphorylation level of endothelial NO synthase (eNOS) on serine1177, and the mRNA levels of endothelin‑1 (ET‑1) were assessed during the experimental procedure. Treatment of the HUVECs with 30 mM glucose and 10‑5 M insulin for 24 h impaired insulin signaling, with reductions in the tyrosine phosphorylation of IR and protein expression of IRS‑1 by almost 75 and 65%, respectively. This, in turn, decreased the activity and phosphorylation of eNOS on serine1177, and reduced the production of NO by almost 80%. By contrast, the mRNA levels of ET‑1 were upregulated. All these changes were ameliorated by atorvastatin. Taken together, these results demonstrated that high concentrations of glucose and insulin impaired insulin signaling leading to endothelial dysfunction, and that atorvastatin ameliorated these changes, acting primarily through the phosphatidylinositol 3-kinase/Akt/eNOS signaling pathway.
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1 

Versari D, Daghini E, Virdis A, Ghiadoni L and Taddei S: Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care. 32(Suppl 2): S314–S321. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Cersosimo E and DeFronzo RA: Insulin resistance and endothelial dysfunction: The road map to cardiovascular diseases. Diabetes Metab Res Rev. 22:423–436. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Davignon J and Ganz P: Role of endothelial dysfunction in atherosclerosis. Circulation. 109(23 Suppl 1): IIII27–III32. 2004. View Article : Google Scholar

4 

Reaven GM: Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 37:1595–1607. 1988. View Article : Google Scholar : PubMed/NCBI

5 

Wheatcroft SB, Williams IL, Shah AM and Kearney MT: Pathophysiological implications of insulin resistance on vascular endothelial function. Diabetic Med. 20:255–268. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Heitzer T, Schlinzig T, Krohn K, Meinertz T and Münzel T: Endothelial dysfunction, oxidative stress and risk of cardiovascular events in patients with coronary artery disease. Circulation. 104:2673–2678. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Ginsberg HN: Insulin resistance and cardiovascular disease. J Clin Invest. 106:453–458. 2000. View Article : Google Scholar

8 

Kubota T, Kubota N, Kumagai H, Yamaguchi S, Kozono H, Takahashi T, Inoue M, Itoh S, Takamoto I, Sasako T, et al: Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle. Cell Metab. 13:294–307. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Rask-Madsen C, Li Q, Freund B, Feather D, Abramov R, Wu IH, Chen K, Yamamoto-Hiraoka J, Goldenbogen J, Sotiropoulos KB, et al: Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice. Cell Metab. 11:379–389. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Kim F, Pham M, Maloney E, Rizzo NO, Morton GJ, Wisse BE, Kirk EA, Chait A and Schwartz MW: Vascular inflammation, insulin resistance and reduced nitric oxide production precede the onset of peripheral insulin resistance. Arterioscler Thromb Vasc Biol. 28:1982–1988. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Okamoto H, Obici S, Accili D and Rossetti L: Restoration of liver insulin signaling in Insr knockout mice fails to normalize hepatic insulin action. J Clin Invest. 115:1314–1322. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Garcia Soriano F, Virág L, Jagtap P, Szabó E, Mabley JG, Liaudet L, Marton A, Hoyt DG, Murthy KG, Salzman AL, et al: Diabetic endothelial dysfunction: The role of poly(ADP-ribose) polymerase activation. Nat Med. 7:108–113. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Rask-Madsen C and King GL: Mechanisms of disease: Endothelial dysfunction in insulin resistance and diabetes. Nat Clin Pract Endocrinol Metab. 3:46–56. 2007. View Article : Google Scholar

14 

Arcaro G, Cretti A, Balzano S, Lechi A, Muggeo M, Bonora E and Bonadonna RC: Insulin causes endothelial dysfunction in humans sites and mechanisms. Circulation. 105:576–582. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Burén J, Liu HX, Lauritz J and Eriksson JW: High glucose and insulin in combination cause insulin receptor substrate-1 and-2 depletion and protein kinase B desensitisation in primary cultured rat adipocytes: Possible implications for insulin resistance in type 2 diabetes. Eur J Endocrinol. 148:157–167. 2003. View Article : Google Scholar

16 

Gelosa P, Cimino M, Pignieri A, Tremoli E, Guerrini U and Sironi L: The role of HMG-CoA reductase inhibition in endothelial dysfunction and inflammation. Vasc Health Risk Manag. 3:567–577. 2007.PubMed/NCBI

17 

Durazzo AE, Machado FS, Ikeoka DT, De Bernoche C, Monachini MC, Puech-Leão P and Caramelli B: Reduction in cardiovascular events after vascular surgery with atorvastatin: A randomized trial. J Vasc Surg. 39:967–975; discussion 975–976. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Chello M, Goffredo C, Patti G, Candura D, Melfi R, Mastrobuoni S, Di Sciascio G and Covino E: Effects of atorvastatin on arterial endothelial function in coronary bypass surgery. Eur J Cardiothorac Surg. 28:805–810. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Cantley LC: The phosphoinositide 3-kinase pathway. Science. 296:1655–1657. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Dilaveris P, Giannopoulos G, Riga M, Synetos A and Stefanadis C: Beneficial effects of statins on endothelial dysfunction and vascular stiffness. Curr Vasc Pharmacol. 5:227–237. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Mahmoud MF, El-Nagar M and El-Bassossy HM: Anti-inflammatory effect of atorvastatin on vascular reactivity and insulin resistance in fructose fed rats. Arch Pharm Res. 35:155–162. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Calisto KL, Carvalho B, Ropelle ER, Mittestainer FC, Camacho AC, Guadagnini D, Carvalheira JB and Saad MJ: Atorvastatin improves survival in septic rats: Effect on tissue inflammatory pathway and on insulin signaling. PLoS One. 5:e142322010. View Article : Google Scholar : PubMed/NCBI

23 

Li X, Shi Y, Wei Y, Ma X, Li Y and Li R: Altered expression profiles of microRNAs upon arsenic exposure of human umbilical vein endothelial cells. Environ Toxicol Pharmacol. 34:381–387. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Schmidt RJ and Baylis C: Total nitric oxide production is low in patients with chronic renal disease. Kidney Int. 58:1261–1266. 2000. View Article : Google Scholar : PubMed/NCBI

25 

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

26 

Lebovitz HE: Insulin resistance-a common link between type 2 diabetes and cardiovascular disease. Diabetes Obes Metab. 8:237–249. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Tousoulis D, Antoniades C, Katsi V, Bosinakou E, Kotsopoulou M, Tsioufis C and Stefanadis C: The impact of early administration of low-dose atorvastatin treatment on inflammatory process, in patients with unstable angina and low cholesterol level. Int J Cardiol. 109:48–52. 2006. View Article : Google Scholar

28 

Tousoulis D, Charakida M, Stefanadi E, Siasos G, Latsios G and Stefanadis C: Statins in heart failure. Beyond the lipid lowering effect. Int J Cardiol. 115:144–150. 2007. View Article : Google Scholar

29 

Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Görgün C, Glimcher LH and Hotamisligil GS: Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 306:457–461. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Hribal ML, Perego L, Lovari S, Andreozzi F, Menghini R, Perego C, Finzi G, Usellini L, Placidi C, Capella C, et al: Chronic hyperglycemia impairs insulin secretion by affecting insulin receptor expression, splicing and signaling in RIN beta cell line and human islets of Langerhans. FASEB J. 17:1340–1342. 2003.PubMed/NCBI

31 

Muniyappa R and Quon MJ: Insulin action and insulin resistance in vascular endothelium. Curr Opin Clin Nutr Metab Care. 10:523–530. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Gonzalez-Gay MA, De Matias JM, Gonzalez-Juanatey C, Garcia-Porrua C, Sanchez-Andrade A, Martin J and Llorca J: Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rheumatoid arthritis. Clin Exp Rheumatol. 24:83–86. 2006.PubMed/NCBI

33 

De Taeye BM, Novitskaya T, McGuinness OP, Gleaves L, Medda M, Covington JW and Vaughan DE: Macrophage TNF-alpha contributes to insulin resistance and hepatic steatosis in diet-induced obesity. Am J Physiol Endocrinol Metab. 293:E713–E725. 2007. View Article : Google Scholar : PubMed/NCBI

34 

López-Sepúlveda R, Gómez-Guzmán M, Zarzuelo MJ, Romero M, Sánchez M, Quintela AM, Galindo P, O'Valle F, Tamargo J, Pérez-Vizcaíno F, et al: Red wine polyphenols prevent endothelial dysfunction induced by endothelin-1 in rat aorta: Role of NADPH oxidase. Clin Sci (Lond). 120:321–333. 2011. View Article : Google Scholar

35 

Zhang H, Zhang J, Ungvari Z and Zhang C: Resveratrol Improves endothelial function: Role of TNF{alpha} and vascular oxidative stress. Arterioscler Thromb Vasc Biol. 29:1164–1171. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Wong V, Stavar L, Szeto L, Uffelman K, Wang CH, Fantus IG and Lewis GF: Atorvastatin induces insulin sensitization in Zucker lean and fatty rats. Atherosclerosis. 184:348–355. 2006. View Article : Google Scholar

37 

Lalli CA, Pauli JR, Prada PO, Cintra DE, Ropelle ER, Velloso LA and Saad MJ: Statin modulates insulin signaling and insulin resistance in liver and muscle of rats fed a high-fat diet. Metabolism. 57:57–65. 2008. View Article : Google Scholar

38 

Calisto KL, Carvalho Bde M, Ropelle ER, Mittestainer FC, Camacho AC, Guadagnini D, Carvalheira JB and Saad MJ: Atorvastatin improves survival in septic rats: Effect on tissue inflammatory pathway and on insulin signaling. PloS One. 5:e142322010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang O, Li J, Chen H, Li J and Kong J: Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin. Mol Med Rep 14: 2791-2798, 2016.
APA
Yang, O., Li, J., Chen, H., Li, J., & Kong, J. (2016). Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin. Molecular Medicine Reports, 14, 2791-2798. https://doi.org/10.3892/mmr.2016.5564
MLA
Yang, O., Li, J., Chen, H., Li, J., Kong, J."Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin". Molecular Medicine Reports 14.3 (2016): 2791-2798.
Chicago
Yang, O., Li, J., Chen, H., Li, J., Kong, J."Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin". Molecular Medicine Reports 14, no. 3 (2016): 2791-2798. https://doi.org/10.3892/mmr.2016.5564
Copy and paste a formatted citation
x
Spandidos Publications style
Yang O, Li J, Chen H, Li J and Kong J: Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin. Mol Med Rep 14: 2791-2798, 2016.
APA
Yang, O., Li, J., Chen, H., Li, J., & Kong, J. (2016). Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin. Molecular Medicine Reports, 14, 2791-2798. https://doi.org/10.3892/mmr.2016.5564
MLA
Yang, O., Li, J., Chen, H., Li, J., Kong, J."Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin". Molecular Medicine Reports 14.3 (2016): 2791-2798.
Chicago
Yang, O., Li, J., Chen, H., Li, J., Kong, J."Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin". Molecular Medicine Reports 14, no. 3 (2016): 2791-2798. https://doi.org/10.3892/mmr.2016.5564
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