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A study of paraoxonase1 (PON1) activities, HDL cholesterol and its association with vascular complication in type 2 diabetes mellitus

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Abstract

The aim of this study is to find out the clinical relevance of estimating serum paraoxonase1 (PON1) arylesterase and PON1 lactonase activity in type 2 diabetes mellitus patients in relation to the development of vascular complications. We have investigated the fasting blood glucose level, HDL cholesterol levels, PON1 arylesterase and PON1 lactonase activities in 80 type 2 diabetes mellitus (DM) patients (DM without complication n = 40, DM with vascular complication n = 40) and compared with 40 healthy age- and sex-matched controls. PON1 arylesterase (ARE) and lactonase (LACT) activities in DM patients with complications (ARE = 60.615 ± 15.510 KU/L, LACT = 18.056 ± 4.215 U/L) are decreased significantly than in DM without complications (ARE = 93.507 ± 21.813 KU/L, LACT = 32.387 ± 8.918 U/L) which are also decreased significantly as compared to controls (ARE = 159.94 ± 45.87 KU/L, LACT = 50.625 ± 6.973 U/L). Logistic regression analysis is applied for assessing predictive utility for diabetic complications demonstrated a significant contribution of PON1 lactonase (Naglekerke’s R 2 = 0.625, AUC = 0.907) and arylesterase (Naglekerke’s R 2 = 0.427, AUC = 0.853) activities. Decreased PON1 lactonase and arylesterase activities may be considered as an additional risk factor for the development of vascular complications in type 2 DM.

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Abbreviations

PON1:

Paraoxonase1

PON2:

Paraoxonase2

PON3:

Paraoxonase3

HDL:

High Density Lipoprotein

HDLc:

High Density Lipoprotein cholesterol

LDL:

Low Density Lipoprotein

DM:

Diabetes Mellitus

ARE:

Arylesterase

LACT:

Lactonase

AUC:

Area under curve

CETP:

Cholesterol ester transport protein

LCAT:

Lecithin Cholesterol acyl transporter

CVA:

Cerebrovascular accidents

PVD:

Peripheral vascular diseases

ECG:

Electrocardiogram

CT:

Computed tomography

References

  1. Zimmet P. Globalization, coca-colonization and the chronic disease epidemic: can the dooms day scenario be averted. J Intern Med. 2001;247:301–10.

    Article  Google Scholar 

  2. Amos A, McCarty D, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabetic Med. 1987;14:S1–S85.

    Google Scholar 

  3. Shaw JE, Sicree RA, Zimmet PZ. Global estimate of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87:4–14.

    Article  CAS  PubMed  Google Scholar 

  4. King H, Aubert R, Herman W. Global burden of diabetes, 1995–2025: prevalence, numerical estimates and projections. Diabetes Care. 1998;21:1414–31.

    Article  CAS  PubMed  Google Scholar 

  5. American Diabetes Association. Diagnosis and classification of diabetes mellitus—2012. Diabetes Care. 2012;35 Suppl 1:S64–71.

    Article  Google Scholar 

  6. Reusch JE. Diabetes, microvascular complications, and cardiovascular complications: what is it about glucose? J Clin Invest. 2003;112:986–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE. The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet. 1993;3:73–6.

    Article  CAS  PubMed  Google Scholar 

  8. Sorenson RC, Bisgaier CL, Aviram M, Hsu C, Billecke S, La Du BN. Human serum paraoxonase/arylesterase’s retained hydrophobic N terminal leader sequence associates with HDLs by binding phospholipids: apolipoprotein A-1 stabilizes activity. Arterioscler Thromb Vasc Biol. 1999;19:2214–25.

    Article  CAS  PubMed  Google Scholar 

  9. Gaidukov L, Tawfik DS. The development of human sera tests for HDL-bound serum PON1 and its lipolactonase activity. J Lipid Res. 2007;48:1637–46.

    Article  CAS  PubMed  Google Scholar 

  10. Mackness M, Mackness B. Paraoxonase 1 and atherosclerosis: is the gene or the protein more important? Free Radic Biol Med. 2004;37:1317–23.

    Article  CAS  PubMed  Google Scholar 

  11. Mackness MI, Arrol S, Abbott C, Durrington PN. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis. 1993;104:129–35.

    Article  CAS  PubMed  Google Scholar 

  12. Mackness MI, Durrington PN. HDL its enzymes and its potential to influence lipid peroxidation. Atherosclerosis. 1995;115:243–53.

    Article  CAS  PubMed  Google Scholar 

  13. Primo-Parmo SL, Sorenson RC, Teiber J, La Du BN. The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics. 1996;33:498–507.

    Article  CAS  PubMed  Google Scholar 

  14. Ng CJ, Shih DM, Hama SY, Villa N, Navab M, Reddy ST. The paraoxonase gene family and atherosclerosis. Free Radic Biol Med. 2005;38:153–63.

    Article  CAS  PubMed  Google Scholar 

  15. Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du BN. Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005;46:1239–47.

    Article  CAS  PubMed  Google Scholar 

  16. Costa LG, Cole TB, Jarvik GP, Furlong CE. Functional genomics of the paraoxonase (PON1) polymorphisms: effects on pesticide sensitivity, cardiovascular disease, and drug metabolism. Annu Rev Med. 2003;54:371–92.

    Article  CAS  PubMed  Google Scholar 

  17. Karabina SA, Lehner AN, Frank E, Parthasarathy S, Santanam N. Oxidative inactivation of paraoxonase—implications in diabetes mellitus and atherosclerosis. Biochim Biophys Acta. 2005;1725:213–21.

    Article  CAS  PubMed  Google Scholar 

  18. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman MA, et al. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest. 1995;96:2882–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest. 1998;101:1581–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mackness B, Hine D, Liu Y, Mastorikou M, Mackness M. Praoxonase-1 oxidized LDL-induced MCP-1 production by endothelial cells. Biochem Biophys Res Commun. 2004;318:680–83.

    Article  CAS  PubMed  Google Scholar 

  21. Aviram M, Rosenblat M, Bisgaier CL. Paraoxonase inhibits high density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest. 1998;101:1581–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Syvänne M, Ahola M, Lahdenperä S, Kahri J, Kuusi T, Virtanen KS, et al. High density lipoprotein subfractions in non insulin-dependent diabetes mellitus and coronary artery disease. J Lipid Res. 1995;36:573–82.

    PubMed  Google Scholar 

  23. Soran H, Hama S, Yadav R, Durrington PN. HDL functionality. Curr Opin Lipidol. 2012;23:353–66.

    Article  CAS  PubMed  Google Scholar 

  24. Bergmeyer HU, Bernt E. Determination of glucose with glucose oxidase and peroxidase. In: Bergmeyer HU, editor. Methods of enzymatic analysis. New York.: Verlag Chemie Academic Press; 1974. p. 1205–15.

    Google Scholar 

  25. Burstein M, Scholnick HR, Morfin R. Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res. 1970;11:583–90.

    CAS  PubMed  Google Scholar 

  26. Mogarekar MR, Chawhan SS. The determination of Q192R polymorphism of paraoxonase 1 using non-toxic substrate p-nitrophenyl acetate. Ind J Hum Genet. 2013;19:71–7.

    Article  CAS  Google Scholar 

  27. Billecke S, Draganov D, Counsell R, Stetson P, Watson C, Hsu C, et al. Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos. 2000;28:1335–42.

    CAS  PubMed  Google Scholar 

  28. Flekač M, Skrha J, Zídková K, Lacinová Z, Hilgertová J. Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus. Physiol Res. 2008;57:717–26.

    PubMed  Google Scholar 

  29. Bansal S, Chawla D, Siddarth M, Banerjee BD, Madhu V, Tripathi A. A study on serum advanced glycation end products and its association with oxidative stress and paraoxonase activity in type 2 diabetic patients with vascular complications. Clin Biochem. 2013;46:109–14.

    Article  CAS  PubMed  Google Scholar 

  30. Bennetts HSE, Chan AK, Holloway B, Karschimkus C, Jenkins AJ, Silink M, et al. Association between PON 1 polymorphisms, PON activity and diabetes complications. J Diabetes Complications. 2006;20:322–28.

    Article  PubMed  Google Scholar 

  31. Letellier C, Durou MR, Jouanolle AM, Le Gall JY, Poirier JY, Ruelland A. Serum paraoxonase activity and paraoxonase gene polymorphism in type 2 diabetic patients with or without vascular complications. Diabetes Metab. 2002;28:297–4.

    CAS  PubMed  Google Scholar 

  32. Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40:406–12.

    Article  Google Scholar 

  33. Hedrick CC, Thrope SR, Fu MX, Harper CM, Yoo J, Kim SM. Glycation impairs high-density lipoprotein function. Diabetologia. 2000;43:312–20.

    Article  CAS  PubMed  Google Scholar 

  34. Friedman A. Advanced glycosylated products and hyperglycemia in the pathogenesis of diabetic complications. Diabetes Care. 1999;22:B65–71.

    Article  PubMed  Google Scholar 

  35. Paolisso G, D’Amore A, Volpe C. Evidence for a relationship between oxidative stress and insulin action in non-insulin dependent type II diabetic patients. Metabolism. 1994;43:1426–29.

    Article  CAS  PubMed  Google Scholar 

  36. Betanzos-Cabrera G, Guerrero-Solano JA, Martínez-Pérez MM, Calderón-Ramos ZG, Belefant-Miller M, Cancino-Diaz JC. Pomegranate juice increases levels of paraoxonase1 (PON1) expression and enzymatic activity in streptozotocin-induced diabetic mice fed with a high-fat diet. Food Res Int. 2011;44:1381–85.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Swami Ramanand Teerth Rural Government Medical College Ambajogai, District Beed, Maharashtra, 431517, India

    Mukund R. Mogarekar, Mahendra G. Dhabe & Chanchal C. Gujrathi

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  1. Mukund R. Mogarekar
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  2. Mahendra G. Dhabe
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  3. Chanchal C. Gujrathi
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Correspondence to Mahendra G. Dhabe.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed written consent was obtained from all individual participants included in the study.

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The authors declare that they have no conflict of interests.

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Mogarekar, M.R., Dhabe, M.G. & Gujrathi, C.C. A study of paraoxonase1 (PON1) activities, HDL cholesterol and its association with vascular complication in type 2 diabetes mellitus. Int J Diabetes Dev Ctries 36, 457–462 (2016). https://doi.org/10.1007/s13410-016-0465-x

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  • DOI: https://doi.org/10.1007/s13410-016-0465-x

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