Importance of glycation in the acceleration of low density lipoprotein (LDL) uptake into macrophages in patients with diabetes mellitus.
BACKGROUND
Two studies were conducted to determine the importance of glycation in the acceleration of low density lipoprotein (LDL) uptake by macrophages in patients with diabetes mellitus.


METHODS
Healthy individuals (n=6) and non-insulin-dependent diabetic patients (n=6) were studied. LDL was separated by sequential ultracentrifugation. Macrophages were collected from the abdominal cavity of ICR-mice and incubated in a medium containing [14C] oleate. In Study 1, LDL from diabetic patients (DM-LDL) and control LDL were then incubated with this medium. The uptake of DM-LDL by macrophages was compared with that of control LDL by measuring the [14C] content of the synthesized cholesteryl ester. In Study 2, glycated LDL was prepared by glycating LDL from 6 healthy individuals in vitro. The uptake of native LDL by macrophages was compared with that of glycated LDL using the same method as in Study 1.


RESULTS
In Study 1, the uptake of DM-LDL (median: 1,405; range: 985-2269 dpm) was significantly higher than that of control LDL (median: 1,095; range: 990-1104 dpm, p<0.05). In Study 2, the uptake of glycated LDL (median: 1,556; range: 889-2837 dpm) was significantly higher than that of native LDL (median: 1,176; range: 789-2098 dpm, p<0.05).


CONCLUSIONS
The results indicate that the greater uptake of DM-LDL than that of control LDL may be attributed to glycation of LDL caused by hyperglycemia in diabetic patients. Glycation of LDL by hyperglycemia may be one cause of the accelerated atherogenesis in diabetic patients.
Makita
T
T
Third Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Tanaka
A
A
Nakano
T
T
Nakajima
K
K
Numano
F
F
D000328:Adult; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006031:Glycosylation; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000493:pharmacokinetics*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008875:Middle Aged
D008077:Lipoproteins, LDL