Summary
Pentosidine is an advanced Maillard/glycation reaction product the formation of which in human skin is significantly increased in Type 1 (insulin-dependent) diabetes mellitus and correlates with the severity of diabetic complications. Preliminary data in a limited number of Type 2 (noninsulin-dependent) diabetic individuals showed that skin pentosidine was not significantly elevated, raising the question of whether statistical power was insufficient for differences to be revealed, or whether pentosidine did not form because biological factors intrinsic to Type 2 diabetes affected the advanced Maillard reaction altogether. To resolve this question, pentosidine levels were measured in 209 human skin samples obtained at autopsy and in purified glomerular basement membranes from 45 subjects of various ages, with and without Type 1 and Type 2 diabetes and uraemia. Pentosidine increased exponentially in skin but curvilinearly in glomerular basement membranes, and reached 75 and 50 pmol/mg collagen at projected 100 years, respectively. Skin levels were not significantly elevated in individuals with Type 2 diabetes (p>0.05). In contrast, pentosidine levels in glomerular basement membranes were elevated above the 95% confidence interval in the majority of diabetic patients regardless of the type of diabetes and in all individuals on haemodialysis. These data clearly demonstrate that the advanced Maillard reaction is indeed accelerated in Type 2 diabetes and strongly suggest that differences in pentosidine accumulation rates may be due to differences in collagen turnover. In diabetes and uraemia, accelerated Maillard reaction mediated protein crosslinking, as reflected by pentosidine, may contribute to decreased turnover of the extracellular matrix, sclerosis and thickening of basement membranes.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Sell DR, Monnier VM (1989) Structure elucidation of a senescence cross-link from human extracellular matrix. J Biol Chem 264: 21547–21602
Sell DR, Monnier VM (1990) End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen. J Clin Invest 85: 380–384
Cohen MP, Carlson EC (1985) Preparation and analysis of glomerular basement membrane. In: Larner J, Pohl SL (eds) Methods in diabetes research. Laboratory methods, Vol I (Part C). Wiley & Sons, New York, pp 357–375
Stegeman H, Stadler K (1967) Determination of hydroxyproline. Clin Chim Acta 18: 267–273
Hamlin CR, Kohn RR (1971) Evidence for progressive age-related structural changes in post mature human collagen. Biochim Biophys Acta 236: 458–467
Neter J, Wasserman W (1974) Applied linear statistical models. Irwin, Homewood, Illinois, pp 21–392
Armitage P (1971) Statistical methods in medical research. Wiley, New York, pp 163–165
Snedecor GW, Cochran WG (1967) Statistical methods. The Iowa State University Press, Ames, Iowa, pp 157–158
Carlson EC, Surerus KK (1986) SEM studies of acellular glomerular basement membrane in human diabetic glomerulopathy. Anat Rec 216: 349–358
Flandin F, Buffevant C, Herbage D (1986) Age-related changes in the biochemical and physicochemical properties of rat skin. Collagen synthesis and maturation and mechanical parameters (uniaxial tension). Cell Mol Biol 32: 565–571
Ohuchi K, Tsurufuji S (1970) Degradation and turnover of collagen in the mouse skin and the effect of whole body X-irradiation. Biochim Biophys Acta 208: 475–481
Gerber G, Gerber G, Altman KI (1960) Studies on the metabolism of tissue proteins. I. Turnover of collagen labelled with proline-U-C14 in young rats. J Biol Chem 235: 2653–2656
Price RG, Spiro RG (1977) Studies on the metabolism of the renal glomerular basement membrane. Turnover measurements in the rat with the use of radiolabelled amino acids. J Biol Chem 23: 8597–8602
Kern P, Moczar M, Robert L (1979) Biosynthesis of skin collagens in normal and diabetic mice. Biochem J 182: 337–345
Kim Y, Kleppel MM, Butowski Ret al. (1991) Differential expression of basement membrane collagen chains in diabetic nephropathy. Am J Pathol 138: 413–420
Schoots AC, Mikkers FEP, Cramers CAMG (1979) Profiling of uremic serum by high-resolution gas chromatography: electron-impact, chemical ionization mass spectrometry. J Chromatogr 164: 1–8
Bergström J, Fürst P (1976) Uremic middle molecules. Clin Nephrol 5: 143–152
Bergström J, Fürst P, Zimmerman L (1979) Uremic middle molecules exist and are biologically active. Clin Nephrol 11: 229–238
Makita Z, Radoff S, Rayfield EJ et al. (1991) Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 325: 836–842
Makita Z, Vlassara H, Cerami A, Bucala R (1992) Immunochemical detection of advanced glycosylation end products in vivo. J Biol Chem 267: 5133–5138
Odetti P, Fogarty J, Sell DR, Monnier VM (1992) Chromatograpic quantitation of plasma and erythrocyte pentosidine in diabetic and uremic subjects. Diabetes 41: 153–159
Hricik DE, Schulak JA, Sell DR, Fogarty JF, Monnier VM (1993) Effects of kidney or kidney-pancreas transplantation on plasma pentosidine. Kidney Int 43: 398–403
National Diabetes Data Group (1979) Classifications and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039–1057
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sell, D.R., Carlson, E.C. & Monnier, V.M. Differential effects of type 2 (non-insulin-dependent) diabetes mellitus on pentosidine formation in skin and glomerular basement membrane. Diabetologia 36, 936–941 (1993). https://doi.org/10.1007/BF02374476
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02374476