Skip to main content
Log in

Intermittent high glucose promotes expression of proinflammatory cytokines in monocytes

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective and design

The aim of this study was to examine expression of proinflammatory cytokines in monocytes under fluctuating glucose conditions.

Material and treatment

Monocytic cells (THP-1) were divided into four groups and cultured in the presence of 5 or 15 mmol/L glucose or in fluctuating conditions (12 h exposure to 15 mmol/L glucose or mannitol medium followed by 12 h exposure to 5 mmol/L glucose or mannitol medium) respectively.

Methods

Levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the supernatants and surface expression of CD11b in monocytes were measured after 72 h culture. Paired Student’s t tests were used to compare two groups and ANOVA for multiple comparisons.

Results

Activation of monocytes was most pronounced in the fluctuating glucose conditions, as measured by concentrations of IL-6 and TNF-α in cultured supernatants and surface expression of CD11b in monocytes (P < 0.05). Fluctuating mannitol also induced a proinflammatory profile, but to a lesser extent than fluctuating glucose.

Conclusions

The results indicated that exposure to fluctuating glucose concentrations enhanced activation of monocytes compared with stable elevation of glucose concentrations. The effects were partly attributable to the inherent osmotic changes.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Grundy Scott M, Benjamin Ivor J, Burke Gregory L, Chait Alan, Eckel Robert H, Howard Barbara V, Mitch William, Smith Sidney C Jr, Sowers James R. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999;100:1134–46.

    PubMed  CAS  Google Scholar 

  2. Temelkova-Kurktschiev TS, Koehler C, Henkel E, Leonhardt W, Fuecker K, Hanafeld M. Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care. 2000;23:1830–4.

    Article  PubMed  CAS  Google Scholar 

  3. Hanefeld M, Fischer S, Julius U, Schulze J, Schwanebeck U, Schmechel H, Ziegelasch HJ, Lindner J. Risk factors for myocardial infarction and death in newly detected NIDDM: the diabetes intervention study 11-year follow-up. Diabetologia. 1996;39:1577–83.

    Article  PubMed  CAS  Google Scholar 

  4. The DECODE Study Group on behalf of the European Diabetes Epidemiology Group. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe. Lancet. 1999; 354:617–21.

    Google Scholar 

  5. Chiasson Jean-Louis, Josse Robert G, Gomis Ramon, Hanefeld Markolf, Karasik Avraham, Laakso Markku. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA. 2003;290:486–94.

    Article  PubMed  CAS  Google Scholar 

  6. Lenters-Westra E, Slingerland RJ. Hemoglobin A1c determination in the A1C-derived average glucose (ADAG) study. Clin Chem Lab Med. 2008;46:1617–23.

    Article  PubMed  CAS  Google Scholar 

  7. Raz Itamar, Wilson Peter WF, Strojek Krzysztof, Kowalska Irina, Bozikov Velimir, Gitt Anselm K, Jermendy György, Campaigne Barbara N, Kerr Lisa, Milicevic Zvonko, Jacober Scott J. Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial. Diabetes Care. 2009;32:381–6.

    Article  PubMed  CAS  Google Scholar 

  8. Shanmugam Narkunaraja, Reddy Marpadga A, Guha Mausumee, Natarajan Rama. High glucose-induced expression of proinflammatory cytokine and chemokine genes in monocytic cells. Diabetes. 2003;52:1256–64.

    Article  PubMed  CAS  Google Scholar 

  9. Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab. 2001;281:E924–30.

    PubMed  CAS  Google Scholar 

  10. Polhill TS, Saad S, Poronnik P, Fulcher GR, Pollock CA. Short-term peaks in glucose promote renal fibrogenesis independently of total glucose exposure. Am J Physiol Renal Physiol. 2004;287:F268–73.

    Article  PubMed  CAS  Google Scholar 

  11. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101:1767–72.

    PubMed  CAS  Google Scholar 

  12. Ferrari R. The role of TNF in cardiovascular disease. Pharmacol Res. 1999;40:97–105.

    Article  PubMed  CAS  Google Scholar 

  13. Nageh Maged F, Sandberg Eric T, Marotti Keith R, Lin Alice H, Melchior Earline P, Bullard Daniel C, Beaudet Arthur L. Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 1997;17:1517–20.

    PubMed  CAS  Google Scholar 

  14. Devaraj S, Jialal I. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radic Biol Med. 2000;29:790–2.

    Article  PubMed  CAS  Google Scholar 

  15. Kulseng B, Skjak-Braek G, Folling I, Espevik T. TNF production from peripheral blood mononuclear cells in diabetic patients after stimulation with alginate and lipopolysaccharide. Scand J Immunol. 1996;43:335–40.

    Article  PubMed  CAS  Google Scholar 

  16. Kunt T, Forst T, Fruh B, Flohr T, Schneider S, Harzer O, Pfutzner A, Engelbach M, Lobig M, Beyer J. Binding of monocytes from normolipidemic hyperglycemic patients with type 1 diabetes to endothelial cells is increased in vitro. Exp Clin Endocrinol Diabetes. 1999;107:252–6.

    Article  PubMed  CAS  Google Scholar 

  17. Azuma Kosuke, Kawamori Ryuzo, Toyofuku Yukiko, Kitahara Yoshiro, Sato Fumihiko, Shimizu Tomoaki, Miura Kyoko, Mine Tomoyuki, Tanaka Yasushi, Mitsumata Masako, Watada Hirotaka. Repetitive fluctuations in blood glucose enhance monocyte adhesion to the endothelium of rat thoracic aorta. Arterioscler Thromb Vasc Biol. 2006;26:2275–80.

    Article  PubMed  CAS  Google Scholar 

  18. Meerschaert J, Furie MB. Monocytes use either CD11/CD18 or VLA-4 to migrate across human endothelium in vitro. J Immunol. 1994;152:1915.

    PubMed  CAS  Google Scholar 

  19. Smith CW, Rothlein R, Hughes BJ, Mariscalco MM, Rudloff HE, Schmalstieg FC, Anderson DC. Recognition of an endothelial determinant for CD18-dependent human neutrophil adherence and transendothelial migration. J Clin Invest. 1988;82(5):1746–56.

    Article  PubMed  CAS  Google Scholar 

  20. Wong TY, Phillips AO, Witowski J, Topley N. Glucose-mediated induction of TGF-1 and MCP-1 in mesothelial cells in vitro is osmolality and polyol pathway dependent. Kidney Int. 2003;63:1404–16.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yang Li-bo.

Additional information

Responsible Editor: Liwu Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li-bo, Y., Wen-bo, Q., Xiao-hong, L. et al. Intermittent high glucose promotes expression of proinflammatory cytokines in monocytes. Inflamm. Res. 60, 367–370 (2011). https://doi.org/10.1007/s00011-010-0279-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-010-0279-0

Keywords

Navigation