Interaction of very-low-density lipoprotein isolated from type I (insulin-dependent) diabetic subjects with human monocyte-derived macrophages.
Very-low-density lipoproteins (VLDL) (density less than 1.006 g/mL) were isolated from type I (insulin-dependent) diabetic patients in good to fair glycemic control and from age-, sex-, and race-matched, nondiabetic, control subjects. VLDL were incubated with human, monocyte-derived macrophages obtained from nondiabetic donors, and the rates of cellular cholesteryl ester synthesis and cholesterol accumulation were determined. VLDL isolated from diabetic patients stimulated significantly more cholesteryl ester synthesis than did VLDL isolated from control subjects (4.04 +/- 1.01 v 1.99 +/- 0.39 nmol 14C-cholesteryl oleate synthesized/mg cell protein/20 h; mean +/- SEM, P less than .05). The stimulation of cholesteryl ester synthesis in macrophages incubated with VLDL isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (P less than .05). The increase in cholesteryl ester synthesis and accumulation in macrophages were mediated by a significant increase in the receptor mediated, high affinity degradation (2.55 +/- 0.23 v 2.12 +/- 0.20 micrograms degraded/mg cell protein/20 h) and accumulation (283 +/- 35 v 242 +/- 33 ng/mg cell protein/20 h) of 125I-VLDL isolated from diabetic patients compared with VLDL from control subjects. To determine if changes in VLDL apoprotein composition were responsible for the observed changes in cellular rates of cholesteryl ester synthesis and accumulation, we also examined the apoprotein composition of the VLDL from both groups. There were no significant differences between the apoproteins B, E, and C content of VLDL from both groups. We also determined the chemical composition of VLDL isolated from both groups of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Klein
R L
RL
Research Service, Veterans Administration Medical Center, Charleston, SC 29403.
Lyons
T J
TJ
Lopes-Virella
M F
MF
D001059:Apoproteins / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000096:biosynthesis / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000302:isolation & purification / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018110:Receptors, Lipoprotein
D001059:Apoproteins; D002788:Cholesterol Esters; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D002784:Cholesterol