Nonenzymatic Glucosylation of High-Density Lipoprotein Accelerates Its Catabolism in Guinea pigs

Nonenzymatic glucosylation of lysine residues of high-density lipoprotein (HDL) was shown to occur in vitro. Most of the incorporated glucose was localized to apoprotein A-l, but other apoproteins were glucosylated as well. Glucosylated high-density lipoproteins (glcHDL) had enhanced electrophoretic mobility on agarose. With increasing amounts of glucose incorporated there was a proportionate increase in the rate of clearance of glcHDL when injected intravenously into guinea pigs. When 60% of lysines were derivatized, clearance of glcHDL was 60% faster than that of control HDL. When as few as 2% of lysines were glucosylated, there was still an 8% increase in the rate of clearance. Uptake of glcHDL by macrophages was not increased. The accelerated clearance of glcHDL from plasma may be relevant to the decreased HDL levels observed in diabetic subjects.