Skip to main content
Article thumbnail
Location of Repository

High glucose disrupts oligosaccharide recognition function via competitive inhibition : a potential mechanism for immune dysregulation in diabetes mellitus

By Rebecca Ilyas, Russell Wallis, Elizabeth J. Soilleux, Paul Townsend, Daniel Zehnder, Bee K. Tan, Robert B. Sim, Hendrik Lehnert, Harpal S. Randeva and Daniel A. Mitchell


Diabetic complications include infection and cardiovascular disease. Within the immune system, host-pathogen and regulatory host-host interactions operate through binding of oligosaccharides by C-type lectin. A number of C-type lectins recognise oligosaccharides rich in mannose and fucose – sugars with similar structures to glucose. This raises the possibility that high glucose conditions in diabetes affect protein-oligosaccharide interactions via competitive inhibition. Mannose binding lectin, soluble DC-SIGN & DC-SIGNR, and surfactant protein D, were tested for carbohydrate binding in the presence of glucose concentrations typical of diabetes, via surface plasmon resonance and affinity chromatography. Complement activation assays were performed in high glucose. DC-SIGN and DC-SIGNR expression in adipose tissues was examined via immunohistochemistry. High glucose inhibited C-type lectin binding to high-mannose glycoprotein and binding of DC-SIGN to fucosylated ligand (blood group B) was abrogated in high glucose. Complement activation via the lectin pathway was inhibited in high glucose and also in high trehalose - a nonreducing sugar with glucoside stereochemistry. DC-SIGN staining was seen on cells with DC morphology within omental and subcutaneous adipose tissues. We conclude that high glucose disrupts C-type lectin function, potentially illuminating new perspectives on susceptibility to infectious and inflammatory disease in diabetes. Mechanisms involve competitive inhibition of carbohydrate-binding within sets of defined proteins, in contrast to broadly indiscriminate, irreversible glycation of proteins

Topics: QP
Publisher: Elsevier
Year: 2011
OAI identifier:

Suggested articles


  1. (2001). A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. doi
  2. (1998). A novel method of purifying lung surfactant proteins A and D from the lung lavage of alveolar proteinosis patients and from pooled amniotic fluid. doi
  3. (2008). Acute modulation of toll-like receptors by insulin. doi
  4. (2007). Advanced glycation endproducts: what is their relevance to diabetic complications? doi
  5. (2002). An endogenous Drosophila receptor for glycans bearing alpha 1,3-linked core fucose residues. doi
  6. (1997). Asymmetry adjacent to the collagen-like domain in rat liver mannose-binding protein.
  7. (2001). Complement. First of two parts.
  8. (2001). Complement. Second of two parts.
  9. (2000). Corpse clearance defines the meaning of cell death.
  10. (2006). DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets. doi
  11. (2006). DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production. doi
  12. DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. doi
  13. (2000). DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. doi
  14. (2000). DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13. doi
  15. (2001). DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans. doi
  16. (2006). Deficiency of mannose-binding lectin greatly increases susceptibility to postburn infection with Pseudomonas aeruginosa. doi
  17. (2005). Functional analysis of the classical, alternative, and MBL pathways of the complement system: standardization and validation of a simple ELISA. doi
  18. (1998). Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. doi
  19. (2007). Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive proinflammatory mediator production. doi
  20. (2000). Identification of DCSIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. doi
  21. (2008). Increased susceptibility of complement factor B/C2 double knockout mice and mannan-binding lectin knockout mice to systemic infection with Candida albicans. doi
  22. (1998). Increased susceptibility of diabetic mice to influenza virus infection: compromise of collectin-mediated host defense of the lung by glucose?
  23. (2008). Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: further evidence of a proinflammatory state. doi
  24. (1995). Lessons from UK prospective diabetes study. doi
  25. Ligand-binding characteristics of rat serum-type mannose-binding protein (MBP-A). Homology of binding site architecture with mammalian and chicken hepatic lectins.
  26. (2009). Lymphocytes in the peritoneum home to the omentum and are activated by resident dendritic cells. doi
  27. (2006). Macrophage-secreted factors induce adipocyte inflammation and insulin resistance. doi
  28. Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome. doi
  29. (2005). Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype. doi
  30. (2005). Mannose-binding lectin: biology and clinical implications. doi
  31. (1996). Mannose-binding lectin: the pluripotent molecule of the innate immune system. doi
  32. (2003). Mannosebinding lectin engagement with late apoptotic and necrotic cells. doi
  33. (2006). Metabolic syndrome and obesity in an insect. doi
  34. (2005). Postprandial hyperglycemia and diabetes complications: is it time to treat? doi
  35. Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin. doi
  36. Recognition of Candida albicans by mannan-binding lectin in vitro and in vivo. doi
  37. (2004). Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR. doi
  38. (2001). Structural basis for selective recognition of oligosaccharides by DC-SIGN and DCSIGNR. doi
  39. (1992). Structure of a Ctype mannose-binding protein complexed with an oligosaccharide. doi
  40. (1981). The basal plasma glucose: a simple relevant index of maturity-onset diabetes. doi
  41. (1998). The C-type lectin superfamily in the immune system. doi
  42. (2008). The lectin-like activity of human C1q and its implication in DNA and apoptotic cell recognition. doi
  43. (2005). TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. doi
  44. (1990). UK Prospective Diabetes Study 7: response of fasting plasma glucose to diet therapy in newly presenting type II diabetic patients, doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.