Diabetologia

, Volume 30, Issue 12, pp 916–923 | Cite as

Stimulation of cholesteryl ester synthesis in human monocyte-derived macrophages by low-density lipoproteins from Type 1 (insulin-dependent) diabetic patients: the influence of non-enzymatic glycosylation of low-density lipoproteins

  • T. J. Lyons
  • R. L. Klein
  • J. W. Baynes
  • H. C. Stevenson
  • M. F. Lopes-Virella
Originals

Summary

Diabetes mellitus is an independent risk factor in the development of atherosclerosis. In this study we aimed to demonstrate whether there is an abnormal interaction between low-density lipoproteins from diabetic patients and human macrophages. We measured cholesteryl ester synthesis and cholesteryl ester accumulation in human monocytederived macrophages (obtained from non-diabetic donors) incubated with low density lipoproteins from Type 1 (insulin-dependent) diabetic patients in good or fair glycaemic control. Low density lipoproteins from the diabetic patients stimulated more cholesteryl ester synthesis than low density lipoproteins from non-diabetic control subjects (7.19±1.19 vs 6.11±0.94 nmol/mg cell protein/20 h, mean±SEM, p<0.05). The stimulation of cholesteryl ester synthesis by low density lipoproteins isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (p<0.02). There were no significant differences in the lipid composition of low density lipoproteins between the diabetic and control groups. Non-enzymatic glycosylation of low density lipoproteins was higher in the diabetic group (p<0.01) and correlated significantly with cholesteryl ester synthesis (r=0.58). Similarly, low-density lipoproteins obtained from non-diabetic subjects and glycosylated in vitro stimulated more cholesteryl ester synthesis in macrophages than control low density lipoproteins. The increase in cholesteryl ester synthesis and accumulation by cells exposed to low density lipoproteins from diabetic patients seems to be mediated by an increased uptake of these lipoproteins by macrophages. This study suggests that glycosylation of low density lipoproteins to the extent occurring in diabetes may alter their interaction with human monocyte-derived macrophages and may lead to increased intracellular cholesteryl ester accumulation. The results suggest a possible mechanism by which hyperglycaemia may contribute to the acceleration of atherosclerosis in diabetes.

Key words

Diabetes LDL metabolism glycosylated LDL cholesteryl ester synthesis human macrophages 

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Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • T. J. Lyons
    • 1
  • R. L. Klein
    • 1
  • J. W. Baynes
    • 2
  • H. C. Stevenson
    • 3
  • M. F. Lopes-Virella
    • 1
  1. 1.Department of MedicineVA Medical Center and Medical University of South CarolinaCharlestonUSA
  2. 2.Department of ChemistryUniversity of South CarolinaColumbiaUSA
  3. 3.Biological Modifiers ProgramNational Cancer Institute, National Institutes of HealthFrederickUSA

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