Glucosylation of Low-Density Lipoproteins to an Extent Comparable to That Seen in Diabetes Slows Their Catabolism

Urs P Steinbrecher; Joseph L Witztum

doi:10.2337/diab.33.2.130

Original Contributions

Glucosylation of Low-Density Lipoproteins to an Extent Comparable to That Seen in Diabetes Slows Their Catabolism

Urs P Steinbrecher and
Joseph L Witztum

Division of Metabolic Disease, Department of Medicine M-013D University of California San Diego, La Jolla, California 92093

Address correspondence to Urs P. Steinbrecher, MD., at the above address.

Diabetes 1984 Feb; 33(2): 130-134. https://doi.org/10.2337/diab.33.2.130

Abstract

In previous studies we have shown that extensive glucosylation of low-density lipoproteins (LDL) (40% of lysines modified) completely blocks receptor-mediated degradation in animals and in man. Other studies indicated that in some diabetics up to 5% of lysine residues of LDL were glucosylated. The present study was done to determine if the extent of glucosylation of LDL which can occur in diabetics could alter LDL catabolism. We measured degradation by cultured normal human fibroblasts and turnover in guinea pigs of various LDLs with 2–17% of lysine residues glucosylated. Modification of as few as 2–5% of lysines decreased LDL catabolism by 5–25%, and the degree of inhibition of catabolism was linearly related to the extent of LDL glucosylation. These results indicate that the extent of LDL glucosylation that can occur in diabetes may slow LDL catabolism and hence increase plasma LDL levels.