Skip to main content
Log in

Differential expression of fructosyllysine-specific receptors on monocytes and macrophages and possible pathophysiological significance

  • Originals
  • Published:
Diabetologia Aims and scope Submit manuscript

Summary

A differing individual expression of fructosyllysine-specific receptors has been found on the monocytes of 90 insulin-dependent diabetic patients and 101 healthy control subjects. The degree of receptor expression is neither age- nor sex-dependent; however, in the diabetic group it correlates significantly with the severity and age of onset of diabetic microangiopathy. To interpret the results of the human study, spontaneously diabetic and non-diabetic BB/OK rats were used to estimate tissue content of glucose-modified proteins and capillary basement membrane thickness in relation to the receptor expression on macrophages. In non-diabetic and diabetic rats no correlation was found between receptor expression and tissue content (i.e. artery, nerve) of fructosyllysine and fluorescent advanced glycation end products. However, animals which express the fructosyllysine receptor showed a greater increase in muscle capillary basement membrane thickness. There are indications that fructosyllysine receptor expression is positively associated with indices of diabetic complications such as microangiopathy and/or capillary basement membrane thickening.

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.

Similar content being viewed by others

Abbreviations

AGE:

Advanced glycation end products

FITC:

fluorescein isothiocynate

FL:

fructosyllysine

GHb:

total glycated haemoglobin

PBS:

phosphate buffered saline

TBS:

Tris buffered saline

CV:

coefficient of variation

References

  1. Williamson JR, Kilo C (1989) Basement membrane in diabetes mellitus. In: Draznin B, Melmed S, LeRoith D (eds) Complications of diabetes mellitus. Liss, New York, pp 19–29

    Google Scholar 

  2. Williamson JR, Tilton RG, Chang K, Kilo C (1988) Basement membrane abnormalities in diabetes mellitus: relationship to clinical microangiopathy. Diab Metabol Rev 4: 339–370

    Article  CAS  Google Scholar 

  3. Raskin P, Rosenstock J (1986) Blood glucose control and diabetic complications. Ann Intern Med 105: 254–263

    Article  CAS  PubMed  Google Scholar 

  4. Larkins RG, Dunlop ME (1992) The link between hyperglycaemia and diabetic nephropathy. Diabetologia 35: 499–504

    Article  CAS  PubMed  Google Scholar 

  5. The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New Engl J Med 329: 977–986

    Article  Google Scholar 

  6. Brownlee M (1995) Advanced protein glycosylation in diabetes and aging. Annu Rev Med 46: 223–234

    Article  CAS  PubMed  Google Scholar 

  7. Baynes JW, Watkins NG, Fisher CI et al. (1989) The Amadori product on protein: structure and reactions. Progr Clin Biol Res 304: 43–68

    CAS  Google Scholar 

  8. Njoroge FG, Monnier VM (1989) The chemistry of the Maillard reaction under physiological conditions. Progr Clin Biol Res 304: 85–107

    CAS  Google Scholar 

  9. Vlassara H (1992) Receptor mediated interactions of advanced glycosylation end products with cellular components within diabetic tissues. Diabetes 41 [Suppl 2]: 52–56

    Article  CAS  PubMed  Google Scholar 

  10. Vlassara H, Brownlee M, Cerami A (1985) High-affinity-receptor-mediated uptake and degradation of glucose-modified proteins: a potential: mechanism for the removal of senescent macromolecules. Proc Natl Acad Sci USA 82: 5588–5592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Vlassara H, Valinsky J, Brownlee M, Cerami C, Nishimoto S, Cerami A (1987) Advanced glycosylation endproducts on erythrocyte cell surface induce receptor-mediated phagocytosis by macrophages. A model of turnover of aging cells. J Exp Med 166: 539–549

    Article  CAS  PubMed  Google Scholar 

  12. Vlassara H, Brownlee M, Monague KR, Dinarello CA, Pasagian A (1988) Cachectin/TNF and IL-1 induced by glucose-modified proteins: role in normal tissue remodeling. Science 240: 1546–1548

    Article  CAS  PubMed  Google Scholar 

  13. Esposito C, Gerlach H, Brett J, Stern D, Vlassara H (1989) Endothelial receptor mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties. J Exp Med 17: 1387–1407

    Article  Google Scholar 

  14. Yan SD, Schmidt AM, Anderson GM et al. (1994) Enhanced cellular oxidant stress by the interaction of advanced glycation endproducts with their receptor-binding proteins. J Biol Chem 269: 9889–9897

    CAS  PubMed  Google Scholar 

  15. Krantz S, Brandt R, Gromoll B (1993) Binding sites for short-term glycated albumin on peritoneal cells of the rat. Biochim Biophys Acta 1177: 15–24

    Article  CAS  PubMed  Google Scholar 

  16. Salazar R, Brandt R, Krantz S (1995) Expression of fructosyllysine receptors on human monocytes and monocyte-like cell lines. Biochim Biophys Acta 1266: 57–63

    Article  PubMed  Google Scholar 

  17. McConahey PJ, Dixon FJ (1966) A method of trace iodination of proteins for immunological studies. Int Arch Allergy 29: 185–189

    Article  CAS  PubMed  Google Scholar 

  18. Costello SM, Felix RT, Giese RW (1979) Enhancement of immune cellular agglutination by use of an avidin-biotin system. Clin Chem 25: 1572–1580

    CAS  PubMed  Google Scholar 

  19. Finot PA, Mauron J (1969) Le blockage de la lysine par la reaction de Maillard: Synthese de N-(desoxy-1-D-fructosyl-1)- et N-(desoxy-1-D-lactulosyl-1)-L-lysine. Helv Chim Acta 52: 1488–1495

    Article  CAS  Google Scholar 

  20. Gilcrease MZ, Hoover RL (1991) Examination of monocyte adherence to endothelium under hyperglycemic conditions. Am J Pathol 139: 11089–11097

    Google Scholar 

  21. Hayes BP, Poulson R, Fitzke FW (1988) Computer measurement of normal and diabetic basement membrane thickness. In: Sakamoto N, Kinoshita JH, Kador PF, Hotta N (eds) Polyol pathway and its role in diabetic complications. Elsevier Amsterdam, pp 300–305

    Google Scholar 

  22. Williamson JR, Vogler NJ, Kilo C (1969) Estimation of vascular basement membrane thickness. Diabetes 18: 567–578

    Article  CAS  PubMed  Google Scholar 

  23. Gottschling HD (1991) Enzymimmunoassay zur Bestimmung von Albumin im Urin. Z med Lab diagn 32: 84–90

    CAS  PubMed  Google Scholar 

  24. Schleicher E, Scheller J, Wieland OH (1981) Quantitation of lysine-bound glucose of normal and diabetic erythrocyte membranes by HPLC analysis of furosine (ε-N-(L-furoyl-methyl)-L-lysine). Biochem Biophys Res Commun 99: 1011–1019

    Article  CAS  PubMed  Google Scholar 

  25. Soulis-Liparota T, Cooper M, Papazoglou D, Clarke B, Jerums G (1991) Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rats. Diabetes 40: 1328–1334

    Article  CAS  PubMed  Google Scholar 

  26. Higgins PJ, Garlick RL, Bunn HF (1982) Glycosylated hemoglobin in human and animal red cells. Role of glucose permeability. Diabetes 31: 743–748

    Article  CAS  PubMed  Google Scholar 

  27. Rendell M, Stephen PM, Paulsen R et al. (1985) An interspecies comparison of normal levels of glycosylated haemoglobin and glycosylated albumin. Comp Biochem Physiol 81B: 819–822

    CAS  Google Scholar 

  28. Deckert T, Poulsen JE, Larsen M (1978) Prognosis of diabetics with diabetic onset before age 31. Diabetologia 14: 463–477

    Article  Google Scholar 

  29. Di Mario U, Pugliese G (1988) Diabetic complications: is there a way out of the labyrinth? Diabetic Complic 2: 163–166

    Article  Google Scholar 

  30. Jennings PE, Barnett AH (1988) New approaches to the pathogenesis and treatment of diabetic microangiopathy. Diabet Med 5: 111–117

    Article  CAS  PubMed  Google Scholar 

  31. Krantz S, Stelter F, Lober M, Gromoll B (1990) Complement component 3 (C3) genetics and diabetes mellitus. Biomed Biochim Acta 49: 1237–1241

    CAS  PubMed  Google Scholar 

  32. Wu V-Y, Cohen MP (1995) Evidence for a ligand receptor system mediating the biologic effects of glycated albumin in glomerular mesangial cells. Biochem Biophys Res Commun 207: 521–528

    Article  CAS  PubMed  Google Scholar 

  33. Krantz S, Salazar R, Brandt R, Kellermann J, Lottspeich F (1995) Purification and partial amino acid sequencing of a fructosyllysine-specific binding protein from cell membranes of the monocyte-like cell line U937. Biochim Biophys Acta 1266: 109–112

    Article  PubMed  Google Scholar 

  34. Kilo C, Vogler N, Williamson JR (1972) Muscle capillary basement membrane changes related to aging and diabetes mellitus. Diabetes 21: 881–905

    Article  CAS  PubMed  Google Scholar 

  35. Williamson JR, Kilo C (1977) Current status of capillary basement membrane disease in diabetes mellitus. Diabetes 26: 65–72

    Article  CAS  PubMed  Google Scholar 

  36. Ellis EN, Mauer M, Goetz FC, Sutherland ER, Steffes MW (1986) Relationship of muscle capillary basement membrane to renal structure and function in diabetes mellitus. Diabetes 35: 421–425

    Article  CAS  PubMed  Google Scholar 

  37. Tilton RG, Hoffmann PL, Kilo C, Williamson JR (1981) Pericyte degeneration and basement membrane thickening in skeletal muscle capillaries of human diabetics. Diabetes 30: 326–334

    Article  CAS  PubMed  Google Scholar 

  38. Yesus WD, Esterly JA, Stuhlman RA, Townsend JF (1976) Significant muscle capillary basement membrane thickening in spontaneously diabeticMystromys albicaudatus. Diabetes 25: 444–449

    Article  CAS  PubMed  Google Scholar 

  39. Itabashi H, Ohneda A, Iimura J (1981) Thickening of basement membrane of muscle capillary in spontaneously diabetic KK mice. Tohoku J Exp Med 133: 339–348

    Article  CAS  PubMed  Google Scholar 

  40. Hayakawa M, Shibata M (1991) The in vitro and in vivo inhibition of protein glycosylation and diabetic vascular basement membrane thickening by pyridoxal-5-phosphate. J Nutr Sci Vitaminol 37: 149–159

    Article  CAS  PubMed  Google Scholar 

  41. Marquie G, Duhault J, Hadjiski P, Petkov P, Bouissou H (1991) Diabetes mellitus in sand rats (Psammomys obesus): microangiopathy during development of the diabetic syndrome. Cell Mol Biol 37: 651–667

    CAS  PubMed  Google Scholar 

  42. Sawada G, Wyse BM, Blanks MC (1986) Morphometric evaluation of capillary basement thickness in the quadriceps muscle of diabetic and nondiabetic Chinese hamsters. Histol Histopathol 1: 1–8

    CAS  PubMed  Google Scholar 

  43. Bloodworth JBM, Engerman RL, Powers KL (1968) Experimental diabetic microangiopathy. I. Basement membrane statistics in the dog. Diabetes 18: 155–158

    Google Scholar 

  44. Yasuda H, Harano Y, Kosugi K et al. (1984) Development of early lesions of microangiopathy in chronically diabetic monkeys. Diabetes 33: 415–420

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brandt, R., Landmesser, C., Vogt, L. et al. Differential expression of fructosyllysine-specific receptors on monocytes and macrophages and possible pathophysiological significance. Diabetologia 39, 1140–1147 (1996). https://doi.org/10.1007/BF02658499

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02658499

Keywords

Navigation