Skip to main content

Advertisement

SpringerLink
Log in

Advanced oxidation protein products in obese women: its relation to insulin resistance and resistin

  • Original
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Obesity is a major risk factor for insulin resistance and type 2 diabetes mellitus (T2DM). Resistin, an adipocyte-secreted hormone, is thought to take a part in the development of insulin resistance and T2DM. The aim of this study was to characterise the changes in circulating levels of resistin and proinflammatory cytokines tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6 in diabetic and prediabetic obese patients and to explore their relationship to insulin resistance. Attempts were also made to see whether resistin levels are related to the degree of oxidative stress, as determined by the measurement of advanced oxidation protein products (AOPPs). The study groups consisted of obese diabetic (BMI: 30–42 kg/m2, n=28) and prediabetic (BMI: 29–41 kg/m2, n=23) women. Fourteen healthy women, with BMI in the range 21.5–25.5 kg/m2, were taken as controls. Serum levels of TNF-a, IL-6, resistin, glucose, insulin and AOPPs were measured. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). Diabetic and prediabetic obese patients had increases in serum resistin and TNF-α levels (P<0.01 and P<0.001, respectively). IL-6 levels in diabetic patients were significantly higher than in prediabetics (P<0.05). AOPP levels were also significantly higher in diabetics than prediabetics and controls (P<0.05 and P<0.001, respectively); and positively correlated with blood glucose. Insulin was significantly associated with circulating resistin and TNF-α. The development of insulin resistance may contribute to the elevation of circulating resistin or vice versa. Determination of AOPPs may be helpful for monitoring the impaired glucose metabolism in obesity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cottam DR, Mattar SG, Barinas-Mitchell E et al (2004) The chronic inflammatory hypothesis for the morbidity associated with morbid obesity: implications and effects of weight loss. Obes Surg 14:589–600

    Article  PubMed  Google Scholar 

  2. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor alpha: direct role in obesity-linked insulin resistance. Science 259:87–91

    Article  PubMed  CAS  Google Scholar 

  3. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19:972–978

    PubMed  CAS  Google Scholar 

  4. Hotamisligil GS, Budavari A, Murray D, Spiegelman BM (1994) Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha. J Clin Invest 94:1543–1549

    Article  PubMed  CAS  Google Scholar 

  5. Mito N, Hosoda T, Kato C, Sato K (2000) Change of cytokine balance in diet-induced obese mice. Metabolism 49:1295–1300

    Article  PubMed  CAS  Google Scholar 

  6. Mooradian AD, Reed RI, Meredith KE, Scuderi P (1991) Serum levels of tumor necrosis factor and IL-1a and IL-1b in diabetic patients. Diabetes Care 14:63–65

    Article  PubMed  CAS  Google Scholar 

  7. Carey AL, Bruce CR, Sacchetti M et al (2004) Interleukin-6 and tumor necrosis factor-alpha are not increased in patients with Type 2 diabetes: evidence that plasma interleukin-6 is related to fat mass and not insulin responsiveness. Diabetologia 47:1029–1037

    PubMed  CAS  Google Scholar 

  8. Bastard JP, Maachi M, Lagathu C et al (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17:4–12

    PubMed  CAS  Google Scholar 

  9. Vettor R, Milan G Rossato M, Federspil G (2005) Review article: adipocytokines and insulin resistance. Aliment Pharmacol Ther 22[Suppl 2]:3–10

    Article  PubMed  CAS  Google Scholar 

  10. Lee JH, Chan JL, Yiannakouris N et al (2003) Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab 88:4848–4856

    Article  PubMed  CAS  Google Scholar 

  11. Savage DB, Sewter CP, Klenk ES et al (2001) Resistin/Fizz 3 expression: in relation to obesity and peroxisome proliferator activated receptor-gamma action in humans. Diabetes 50:2199–2202

    Article  PubMed  CAS  Google Scholar 

  12. Zhang JL, Qin YW, Zheng X et al (2003) Serum resistin level in essential hypertension patients with different glucose tolerance. Diabetic Med 20:828–831

    Article  PubMed  CAS  Google Scholar 

  13. Kusminski CM, McTernan PG, Kumar S (2005) Role of resistin in obesity, insulin resistance and Type II diabetes. Clin Sci (Lond) 109:243–256

    Article  CAS  Google Scholar 

  14. Steppan CM, Bailey ST, Bhat S et al (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312

    Article  PubMed  CAS  Google Scholar 

  15. Fantuzzi G (2005) Adipose tissue, adipokines and inflammation. J Allergy Clin Immunol 115:911–919

    Article  PubMed  CAS  Google Scholar 

  16. Chanchay S, Tungtrongchitr R, Harnroongroj T et al (2006) Plasma resistin, insulin concentration in non-diabetic and diabetic, overweight/obese Thai. Int J Vitam Nutr Res 76:125–131

    Article  PubMed  CAS  Google Scholar 

  17. Silha JV, Krsek M, Skrha JV et al (2003) Plasma resistin, adiponectin and leptin levels in lean and obese subjects: Correlations with insulin resistance. Eur J Endocrinol 149:331–335

    Article  PubMed  CAS  Google Scholar 

  18. Qi Y, Nie Z, Lee YS et al (2006) Loss of resistin improves glucose homeostasis in leptin deficiency. Diabetes 55:3083–3090

    Article  PubMed  CAS  Google Scholar 

  19. Yaturu S, Daberry RP, Rains J, Jain S (2006) Resistin and adiponectin levels in subjects with coronary artery disease and type 2 diabetes. Cytokine 34:219–223

    Article  PubMed  CAS  Google Scholar 

  20. Kougias P, Chai H, Lin PH et al (2005) Adipocyte-derived cytokine resistin causes endothelial dysfunction of porcine coronary arteries. J Vasc Surg 41:691–698

    Article  PubMed  Google Scholar 

  21. Bo S, Gambino R, Pagani A et al (2005) Relationships between human serum resistin, inflammatory markers and insulin resistance. Int J Obes 29:1315–1320

    Article  CAS  Google Scholar 

  22. Opara EC (2002) Oxidative stress, micronutrients, diabetes mellitus and its complications. J R Soc Health 122:28–34

    Article  PubMed  CAS  Google Scholar 

  23. Martin-Gallan P, Carrascosa A, Gussinye M, Dominguez C (2003) Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications. Free Radic Biol Med 34:1563–1574

    Article  PubMed  CAS  Google Scholar 

  24. Gil-Del Valle L, Milian LC, Toledo A et al (2005) Altered redox status in patients with diabetes mellitus type I. Pharmacol Res 51:375–380

    Article  PubMed  CAS  Google Scholar 

  25. Davi G, Falco A, Patrono C (2005) Lipid peroxidation in diabetes mellitus. Antioxid Redox Signal 7:256–268

    Article  PubMed  CAS  Google Scholar 

  26. Furukawa S, Fujita T, Shimabukuro M et al (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114:1752–1761

    PubMed  CAS  Google Scholar 

  27. Witko-Sarsat V, Friedlander M, Capeiller-Blandin C (1996) AOPP as a novel marker of oxidative stress in uremia. Kidney Int 49:1304–1313

    Article  PubMed  CAS  Google Scholar 

  28. Kaluosava M, Skrha J, Zima T (2002) Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res 51:597–604

    Google Scholar 

  29. Atabek ME, Keskin M, Yazici C et al (2006) Protein oxidation in obesity and insulin resistance. Eur J Pediatr 165:753–756

    Article  PubMed  CAS  Google Scholar 

  30. American Diabetes Association (2007) Diagnosis and classification of diabetes mellitus. Diabetes Care 30:S42–S47

    Article  CAS  Google Scholar 

  31. Matthews DR, Hosker JP, Rudenski AS et al (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  PubMed  CAS  Google Scholar 

  32. Osawa H, Yamada K, Onuma H et al (2004) The G/G genotype of a resistin single-nucleotide polymorphism at −420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3. Am J Hum Genet 75:678–686

    Article  PubMed  CAS  Google Scholar 

  33. Gillery P (2001) Advanced glycation end products (AGEs), free radicals and diabetes. J Soc Biol 195:387–390

    PubMed  CAS  Google Scholar 

  34. De Cristofaro R, Rocca B, Vitacolonna E et al (2003) Lipid and protein oxidation contribute to a prothrombotic state in patients with type 2 diabetes mellitus. J Thromb Haemost 1:250–256

    Article  PubMed  Google Scholar 

  35. Yudkin JS, Kumari M, Humpries SE, Mohammed-Ali V (2000) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148:209–214

    Article  PubMed  CAS  Google Scholar 

  36. Tuttle HA, Davis-Gorman G, Goldman S et al (2004) Proinflammatory cytokines are increased in type 2 diabetic women with cardiovascular disease. J Diabetes Complications 18:343–351

    Article  PubMed  Google Scholar 

  37. Zinman B, Hanley AJ, Harris SB et al (1999) Circulating tumor necrosis factor-alpha concentrations in a native Canadian population with a high rate of type 2 diabetes mellitus. J Clin Endocrinol Metab 84:272–278

    Article  PubMed  CAS  Google Scholar 

  38. Hu FB, Meigs JB, Li TY et al (2004) Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53:693–700

    Article  PubMed  CAS  Google Scholar 

  39. Sjöholm A, Nyström T (2006) Inflammation and the etiology of type 2 diabetes. Diabetes Metab Res Rev 22:4–10

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Çapa, 34093, Istanbul, Turkey

    H. Koçak, F. Gürdöl, P. Öner & R. Süzme

  2. Medical Services Training School, Medical Laboratory Programme, Istanbul University, Cerrahpaşa, Istanbul, Turkey

    Y. Öner-İyidoğan

  3. Division of Internal Diseases, Taksim Training and Educational Hospital, Taksim, 34433, Istanbul, Turkey

    D. Esin

  4. Department of Public Health, Istanbul Faculty of Medicine, Istanbul University, Çapa, 34093, Istanbul, Turkey

    H. İşsever

Authors
  1. H. Koçak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Öner-İyidoğan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Gürdöl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Öner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Süzme
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Esin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. İşsever
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. Gürdöl.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koçak, H., Öner-İyidoğan, Y., Gürdöl, F. et al. Advanced oxidation protein products in obese women: its relation to insulin resistance and resistin. Clin. Exper.Med. 7, 173–178 (2007). https://doi.org/10.1007/s10238-007-0143-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-007-0143-x

Key words

Search

Navigation