Skip to main content

Advertisement

Log in

Assessment of human lymphocyte proliferation associated with metabolic syndrome

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background

Metabolic syndrome (MetS), a cluster of various metabolic conditions, has become epidemic and causes increased morbidity and mortality.

Purpose

The aim of this study was to compare lymphocyte proliferation under two different stimuli, Concanavalin A (ConA) and insulin, in a group of patients with MetS (Group 1) and a healthy group (Group 2).

Methods

Group 1 consisted of 53 patients who met the diagnostic criteria for MetS. Group 2 consisted of 63 patients without MetS. All individuals were evaluated for lipid profile and glycemia. Lymphocyte extraction and culture were performed for each subject and lymphocyte proliferation was assessed using the Alamar blue technique.

Results

There was no gender difference between both groups, but in terms of age, there was a significant difference. The use of Con A at concentrations of 1 and 5 µg/mL induced a high lymphocyte proliferation in both groups. In contrast, when different concentrations of insulin were added, no significant changes in lymphocyte proliferation were observed. However, the proliferation of lymphocytes was significantly higher in Group 1 compared to Group 2 under insulin stimulus, which did not happen under ConA stimulation. Even after age and gender correction, this difference was maintained.

Conclusions

The increased lymphocyte proliferative response to insulin in patients with MetS found in this study suggests a role of the lymphocyte response to insulin in the pathophysiology of MetS. This response may be used as an immuno-biological marker for MetS, although further studies to evaluate its clinical usefulness need to be conducted.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Edwards KL, Hutter CM, Wan JY, Kim H, Monks SA (2008) Genome-wide linkage scan for the metabolic syndrome: the GENNID study. Obesity 16(7):1596–1601. doi:10.1038/oby.2008.236

    Article  CAS  PubMed  Google Scholar 

  2. Antonopoulos S (2002) Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation 106(25):3143–3421

    Google Scholar 

  3. Ford ES, Giles WH, Dietz WH (2002) Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287(3):356–359

    Article  PubMed  Google Scholar 

  4. López-Jaramillo P, Pradilla LP, Castillo VR, Lahera V (2007) Socioeconomic pathology as a cause of regional differences in the prevalence of metabolic syndrome and pregnancy-induced hypertension. Rev Esp Cardiol (English Edition) 60(2):168–178

    Google Scholar 

  5. Manzur F, Alvear C, Alayón A (2008) Caracterización fenotípica y metabólica del síndrome metabólico en Cartagena de Indias; Phenotypic and metabolic characterization of the metabolic syndrome in Cartagena de Indias. Rev Colomb Cardiol 15(3):97–101

    Google Scholar 

  6. Scott R, Donoghoe M, Watts GF, O’Brien R, Pardy C, Taskinen MR, Davis TM, Colman PG, Manning P, Fulcher G, Keech AC, Investigators FS (2011) Impact of metabolic syndrome and its components on cardiovascular disease event rates in 4900 patients with type 2 diabetes assigned to placebo in the FIELD randomised trial. Cardiovasc Diabeto 10:102. doi:10.1186/1475-2840-10-102

    Article  CAS  Google Scholar 

  7. Yun JE, Won S, Sung J, Jee SH (2012) Impact of metabolic syndrome independent of insulin resistance on the development of cardiovascular disease. Circul J 76(10):2443–2448

    Article  CAS  Google Scholar 

  8. Centers for Disease Control and Prevention (CDC) (2011) National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States. US Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta

    Google Scholar 

  9. American Diabetes Association (2010) Standards of medical care in diabetes–2014 (2014). Diabetes Care 37(Suppl 1):S14–S80

    Google Scholar 

  10. Pasini E, Flati V, Paiardi S, Rizzoni D, Porteri E, Aquilani R, Assanelli D, Corsetti G, Speca S, Rezzani R, De Ciuceis C, Agabiti-Rosei E (2010) Intracellular molecular effects of insulin resistance in patients with metabolic syndrome. Cardiovasc Diabetol 9:46. doi:10.1186/1475-2840-9-46

    Article  PubMed Central  PubMed  Google Scholar 

  11. Chang FY, Shaio MF (1995) Decreased cell-mediated immunity in patients with non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 28(2):137–146

    Article  CAS  PubMed  Google Scholar 

  12. Stentz FB, Kitabchi AE (2007) Transcriptome and proteome expressions involved in insulin resistance in muscle and activated T-lymphocytes of patients with type 2 diabetes. Genomics Proteomics Bioinform 5(3–4):216–235. doi:10.1016/S1672-0229(08)60009-1

    Article  CAS  Google Scholar 

  13. Lao XQ, Neil Thomas G, Jiang C, Zhang W, Adab P, Lam TH, Cheng KK (2008) White blood cell count and the metabolic syndrome in older Chinese: the Guangzhou Biobank Cohort Study. Atherosclerosis 201(2):418–424. doi:10.1016/j.atherosclerosis.2007.12.053

    Article  CAS  PubMed  Google Scholar 

  14. Otton R, Carvalho CR, Mendonca JR, Curi R (2002) Low proliferation capacity of lymphocytes from alloxan-diabetic rats: involvement of high glucose and tyrosine phosphorylation of Shc and IRS-1. Life Sci 71(23):2759–2771

    Article  CAS  PubMed  Google Scholar 

  15. Duffaut C, Zakaroff-Girard A, Bourlier V, Decaunes P, Maumus M, Chiotasso P, Sengenes C, Lafontan M, Galitzky J, Bouloumie A (2009) Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol 29(10):1608–1614. doi:10.1161/ATVBAHA.109.192583

    Article  CAS  PubMed  Google Scholar 

  16. Piatkiewicz P, Czech A, Taton J, Gorski A (2010) Investigations of cellular glucose transport and its regulation under the influence of insulin in human peripheral blood lymphocytes. Endokrynol Pol 61(2):182–187

    CAS  PubMed  Google Scholar 

  17. Stone KD, Feldman HA, Huisman C, Howlett C, Jabara HH, Bonilla FA (2009) Analysis of in vitro lymphocyte proliferation as a screening tool for cellular immunodeficiency. Clin Immunol 131(1):41–49. doi:10.1016/j.clim.2008.11.003

    Article  CAS  PubMed  Google Scholar 

  18. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr, International Diabetes Federation Task Force on E, Prevention, National Heart L, Blood I, American Heart A, World Heart F, International Atherosclerosis S, International Association for the Study of O (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120(16):1640–1645. doi:10.1161/CIRCULATIONAHA.109.192644

    Article  CAS  PubMed  Google Scholar 

  19. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ, Joint National Committee on Prevention DE, Treatment of High Blood Pressure. National Heart L, Blood I, National High Blood Pressure Education Program Coordinating C (2003) Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 42(6):1206–1252. doi:10.1161/01.HYP.0000107251.49515.c2

    Article  CAS  PubMed  Google Scholar 

  20. NIH, Nhlbi, OEI (2000) The practical guide: identification, evaluation and treatment of overweight and obesity in adults. Initiative NOE, Bethesda

    Google Scholar 

  21. Hawrylowicz CM, Klaus GG (1984) Activation and proliferation signals in mouse B cells IV Concanavalin A stimulates B cells to leave G0, but not to proliferate. Immunology 53(4):703–711

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Palacios R (1982) Concanavalin A triggers T lymphocytes by directly interacting with their receptors for activation. J Immunol 128(1):337–342

    CAS  PubMed  Google Scholar 

  23. Tchorzewski H, Glowacka E, Banasik M, Lewkowicz P, Szalapska-Zawodniak M (2001) Activated T lymphocytes from patients with high risk of type I diabetes mellitus have different ability to produce interferon-gamma, interleukin-6 and interleukin-10 and undergo anti-CD95 induced apoptosis after insulin stimulation. Immunol Lett 75(3):225–234

    Article  CAS  PubMed  Google Scholar 

  24. Kim DJ, Noh JH, Lee BW, Choi YH, Chung JH, Min YK, Lee MS, Lee MK, Kim KW (2008) The associations of total and differential white blood cell counts with obesity, hypertension, dyslipidemia and glucose intolerance in a Korean population. J Korean Med Sci 23(2):193–198. doi:10.3346/jkms.2008.23.2.193

    Article  PubMed Central  PubMed  Google Scholar 

  25. Kim JA, Choi YS, Hong JI, Kim SH, Jung HH, Kim SM (2006) Association of metabolic syndrome with white blood cell subtype and red blood cells. Endocr J 53(1):133–139

    Article  PubMed  Google Scholar 

  26. Tanigawa T, Iso H, Yamagishi K, Muraki I, Kawamura N, Nakata A, Sakurai S, Ohira T, Shimamoto T (2004) Association of lymphocyte sub-populations with clustered features of metabolic syndrome in middle-aged Japanese men. Atherosclerosis 173(2):295–300. doi:10.1016/j.atherosclerosis.2003.12.019

    Article  CAS  PubMed  Google Scholar 

  27. Phillips AC, Carroll D, Gale CR, Drayson M, Thomas GN, Batty GD (2010) Lymphocyte sub-population cell counts are associated with the metabolic syndrome and its components in the Vietnam experience study. Atherosclerosis 213(1):294–298. doi:10.1016/j.atherosclerosis.2010.08.047

    Article  CAS  PubMed  Google Scholar 

  28. Shim WS, Kim HJ, Kang ES, Ahn CW, Lim SK, Lee HC, Cha BS (2006) The association of total and differential white blood cell count with metabolic syndrome in type 2 diabetic patients. Diabetes Res Clin Pract 73(3):284–291. doi:10.1016/j.diabres.2006.02.001

    Article  CAS  PubMed  Google Scholar 

  29. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15(8):930–939. doi:10.1038/nm.2002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Okamoto Y, Folco EJ, Minami M, Wara AK, Feinberg MW, Sukhova GK, Colvin RA, Kihara S, Funahashi T, Luster AD, Libby P (2008) Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res 102(2):218–225. doi:10.1161/CIRCRESAHA.107.164988

    Article  CAS  PubMed  Google Scholar 

  31. Wu H, Perrard XD, Wang Q, Perrard JL, Polsani VR, Jones PH, Smith CW, Ballantyne CM (2010) CD11c expression in adipose tissue and blood and its role in diet-induced obesity. Arterioscler Thromb Vasc Biol 30(2):186–192. doi:10.1161/ATVBAHA.109.198044

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Erdem A, Uenishi M, Kucukdurmaz Z, Matsumoto K, Kato R, Hara M, Yazici M (2012) The effect of metabolic syndrome on heart rate turbulence in non-diabetic patients. Cardiol J 19(5):507–512

    Article  PubMed  Google Scholar 

  33. Federici M, Menghini R, Mauriello A, Hribal ML, Ferrelli F, Lauro D, Sbraccia P, Spagnoli LG, Sesti G, Lauro R (2002) Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells. Circulation 106(4):466–472

    Article  CAS  PubMed  Google Scholar 

  34. Rask-Madsen C, Li Q, Freund B, Feather D, Abramov R, Wu IH, Chen K, Yamamoto-Hiraoka J, Goldenbogen J, Sotiropoulos KB, Clermont A, Geraldes P, Dall’Osso C, Wagers AJ, Huang PL, Rekhter M, Scalia R, Kahn CR, King GL (2010) Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice. Cell Metab 11(5):379–389. doi:10.1016/j.cmet.2010.03.013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Gallagher EJ, LeRoith D (2013) Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic syndrome with cancer. Diabetes Care 36(Suppl 2):S233–S239. doi:10.2337/dcS13-2001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Cusi K, Maezono K, Osman A, Pendergrass M, Patti ME, Pratipanawatr T, DeFronzo RA, Kahn CR, Mandarino LJ (2000) Insulin resistance differentially affects the PI 3-kinase—and MAP kinase—mediated signaling in human muscle. J Clin Investig 105(3):311–320. doi:10.1172/JCI7535

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Parpal S, Karlsson M, Thorn H, Stralfors P (2001) Cholesterol depletion disrupts caveolae and insulin receptor signaling for metabolic control via insulin receptor substrate-1, but not for mitogen-activated protein kinase control. J Biol Chem 276(13):9670–9678. doi:10.1074/jbc.M007454200

    Article  CAS  PubMed  Google Scholar 

  38. Zachurzok-Buczynska A, Klimek K, Firek-Pedras M, Malecka-Tendera E (2011) Are metabolic syndrome and its components in obese children influenced by the overweight status or the insulin resistance? Endokrynol Pol 62(2):102–108

    CAS  PubMed  Google Scholar 

  39. Walker SE, Gurka MJ, Oliver MN, Johns DW, DeBoer MD (2012) Racial/ethnic discrepancies in the metabolic syndrome begin in childhood and persist after adjustment for environmental factors. Nutr Metab Cardiovasc Dis 22(2):141–148. doi:10.1016/j.numecd.2010.05.006

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Marquez-Sandoval F, Macedo-Ojeda G, Viramontes-Horner D, Fernandez Ballart JD, Salas Salvado J, Vizmanos B (2011) The prevalence of metabolic syndrome in Latin America: a systematic review. Public Health Nutr 14(10):1702–1713. doi:10.1017/S1368980010003320

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge financial support from Universidad Tecnológica de Pereira (Grant 5-11-12, Pereira, Colombia) and COLCIENCIAS (Contrato 220-2010, Bogotá, Colombia).

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

This study was approved by the Bioethics Committee of the Universidad Tecnológica de Pereira. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation at Universidad Tecnológica de Pereira.

Informed consent

A written informed consent was obtained from each participant in this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to O. A. Pinzón.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pinzón, O.A., Sánchez, J.C., Sepúlveda-Arias, J.C. et al. Assessment of human lymphocyte proliferation associated with metabolic syndrome. J Endocrinol Invest 38, 1277–1282 (2015). https://doi.org/10.1007/s40618-015-0307-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-015-0307-6

Keywords

Navigation