Isolation, characterization, and metabolism of the glycated and nonglycated subfractions of low-density lipoproteins isolated from type I diabetic patients and nondiabetic subjects.
The total low-density lipoprotein (LDL) fraction was isolated from 21 patients with type I diabetes and 7 nondiabetic normolipemic subjects. The LDL was separated into two subfractions, one glycated (G-LDL) and one nonglycated (N-LDL), using affinity chromatography. G-LDL comprised 21.1 +/- 3.6 and 5.2 +/- 0.6% of the total LDL in diabetic patients and normal subjects, respectively. G-LDL isolated from both diabetic patients and normal subjects was significantly more glycated than N-LDL isolated from the same subject. G-LDL isolated from both diabetic patients and normal subjects was enriched in triglycerides. The metabolism of N-LDL and G-LDL was investigated in human fibroblasts, which express only the classical LDL receptor, and in human monocyte-derived macrophages, which also express a receptor for G-LDL. In fibroblasts, the rates of receptor-mediated accumulation of N-LDL isolated from normal subjects and diabetic patients were significantly greater (P < 0.01) than those of G-LDL. In contrast, when the same LDL subfractions were incubated with human monocyte-derived macrophages, the rates of receptor-mediated accumulation of G-LDL isolated from both groups were significantly greater (P < 0.01) than those of N-LDL. Rates of degradation of G-LDL by human macrophages were not significantly different from those of N-LDL during short-term incubations but reached statistical significance (P < 0.05) when LDL subfractions were incubated with cells for 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Klein
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RL
Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina 29401, USA.
Laimins
M
M
Lopes-Virella
M F
MF
D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D002846:Chromatography, Affinity; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010743:Phospholipids / Q000097:blood; D011973:Receptors, LDL / Q000378:metabolism*; D012016:Reference Values; D012867:Skin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D000093844:Glycated Proteins
D002784:Cholesterol; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D010743:Phospholipids; D011973:Receptors, LDL; D014280:Triglycerides; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins