Nonenzymatic glycosylation of HDL and impaired HDL-receptor-mediated cholesterol efflux

Paul Duell, John F. Oram, Edwin L. Bierman

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Previous studies have shown that nonenzymatic glycosylation of high-density lipoprotein (HDL) inhibits high-affinity binding to cultured cells and the candidate HDL-receptor protein. Because binding of HDL to its receptor is required for HDL-receptor-mediated cholesterol efflux from cells, we hypothesized that glycosylated HDL3 would have reduced ability to remove cholesterol from cells. HDL3 was glycosylated in vitro to achieve up to 40-50% reductions in free-lysine residues. Glycosylated HDL3 had a slightly greater ability than control HDL3 to sequester cholesterol directly from the plasma membrane, as predicted by changes in lipid composition. This process is independent of HDL-receptor binding and should not be influenced by reduced binding of HDL3. In contrast, efflux of intracellular cholesterol from cells, which is HDL-receptor dependent, was reduced 25-40%. The ability of glycosylated HDL3 to diminish cholesterol esterification was significantly reduced, indicating reduced net cholesterol efflux. Steady-state efflux of LDL-derived cholesterol was also markedly reduced. These findings suggest that nonenzymatically glycosylated HDL is functionally abnormal and might contribute to the accelerated development of atherosclerosis in patients with diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)377-384
Number of pages8
JournalDiabetes
Volume40
Issue number3
StatePublished - Mar 1991

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HDL Lipoproteins
Glycosylation
Cholesterol
Esterification
LDL Cholesterol
Lysine
high density lipoprotein receptors
Cultured Cells
Atherosclerosis
Diabetes Mellitus
Cell Membrane
Lipids
Proteins

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Nonenzymatic glycosylation of HDL and impaired HDL-receptor-mediated cholesterol efflux. / Duell, Paul; Oram, John F.; Bierman, Edwin L.

In: Diabetes, Vol. 40, No. 3, 03.1991, p. 377-384.

Research output: Contribution to journalArticle

Duell, Paul ; Oram, John F. ; Bierman, Edwin L. / Nonenzymatic glycosylation of HDL and impaired HDL-receptor-mediated cholesterol efflux. In: Diabetes. 1991 ; Vol. 40, No. 3. pp. 377-384.
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