Two-dimensional stress-relaxation behavior of human skin as influenced by non-enzymatic glycation and the inhibitory agent aminoguanidine

J Biomech. 1998 Nov;31(11):985-93. doi: 10.1016/s0021-9290(98)00088-8.


In order to simulate the in vivo stress alterations of diabetic skin in an in vitro model, we examined the viscoelastic properties of long-term glycated human skin samples. Since skin is subjected to biaxial tension, we used two-dimensional multiaxial testing which better reflects the in vivo situation than the uniaxial testing mode. For native skin samples from the abdominal region we found a direction-dependent elastic stress strain behavior. The viscous stress component was separated from the elastic stress component by relaxation tests at consecutive incremental steps of radial strains. We hypothesize that glycation-induced changes in the tissue stiffness are generated in a direction-dependent mode. A marked increase of the direction-dependent stiffness was found upon long-term incubation with glucose-6-phosphate. This increase was statistically significant for the maximum principal elastic stress component which was highly correlated with the degree of non-enzymatic collagen modification. The viscous fractions obtained from two-dimensional relaxation tests at consecutive radial strains were inversely correlated with non-enzymatic modification. Only at 30% radial strain a significant decrease of the viscous fraction engendered by glucose-6-phosphate was observed together with a direction-dependent significant increase of the expectation value of the time constant. The biomechanical and biochemical effects of long-term glycation could be partially reversed by aminoguanidine, a potential therapeutic agent for patients with diabetes mellitus. Our findings suggest that additional cross-links generated by long-term glycation cause two-dimensional biomechanical alterations in human skin, which can be unequivocally detected by multiaxial testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomechanical Phenomena
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / physiopathology*
  • Elasticity
  • Enzyme Inhibitors / pharmacology
  • Glucose-6-Phosphate / pharmacology
  • Glycation End Products, Advanced / metabolism
  • Glycosylation
  • Guanidines / pharmacology*
  • Humans
  • In Vitro Techniques
  • Mathematics
  • Middle Aged
  • Rheology
  • Skin Physiological Phenomena* / drug effects
  • Stress, Mechanical
  • Viscosity


  • Enzyme Inhibitors
  • Glycation End Products, Advanced
  • Guanidines
  • Glucose-6-Phosphate
  • pimagedine