Glycation of very low density lipoprotein from rat plasma impairs its catabolism.
Rat VLDL were glycated in vitro in the presence or absence of a reducing agent. Prior to glycation, the VLDL triglyceride was endogenously radiolabelled with [3H]-oleic acid. Post glycation the VLDL B-apoprotein was exogenously radiolabelled with [131]I. The double labelled VLDL was then injected into normal rats and the decline in plasma radioactivity of the two isotopes was used as a measure of triglyceride and particle clearance. VLDL glycated in either the presence or absence of reducing agent exhibited a significantly slower removal of triglyceride and apoprotein B compared to normal VLDL. The ability of glycated VLDL triglyceride to act as substrate for lipoprotein lipase and hepatic lipase was examined. Increasing concentrations of normal and glycated VLDL triglyceride were incubated with post-heparin plasma. The kinetics of triglyceride hydrolysis were determined in a manner analogous to Michaelis-Menten analysis. Glycated VLDL was found to be poorer than normal VLDL as a substrate for lipoprotein lipase. Glycation of VLDL appears to interfere with the lipolysis of its triglyceride. This may explain the delayed clearance of glycated VLDL triglyceride in vivo. Glycation also extended the mean plasma residence time of the VLDL particle. These factors may, in part, contribute to the hypertriglyceridaemia observed in subjects with diabetes mellitus.
Mamo
J C
JC
Department of Medicine, Toronto General Hospital, Ontario, Canada.
Szeto
L
L
Steiner
G
G
D000818:Animals; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006868:Hydrolysis; D007700:Kinetics; D008066:Lipolysis; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D000093844:Glycated Proteins
D005947:Glucose; D017127:Glycation End Products, Advanced; D008079:Lipoproteins, VLDL; D019301:Oleic Acid; D009829:Oleic Acids; D014280:Triglycerides; C047671:glycated lipoproteins, VLDL; D000093844:Glycated Proteins