The effect of low density lipoprotein composition on the regulation of cellular cholesterol synthesis: a comparison in diabetic and non-diabetic subjects.
This study investigates compositional differences in low density lipoprotein (LDL) subfractions and their relationship to cellular cholesterol synthesis. We examined ten normocholesterolaemic (serum cholesterol < 6.5 mM) non-diabetic subjects (group 1) and compared them with ten normocholesterolaemic (group 2) and ten hypercholesterolaemic (group 3) (serum cholesterol > 6.5 mM) type 2 (non-insulin-dependent) diabetic patients. Serum cholesterol levels for groups 1, 2 and 3 were 5.19 +/- 0.27, 5.20 +/- 0.27 and 7.51 +/- 0.31 mM. LDL (density 1.006-1.028 g/l) and LDL2 (1.028-1.063 g/l) were isolated by density gradient ultracentrifugation. A significantly greater proportion of cholesterol was carried in LDL2 than LDL1 in all groups. There was a significantly lower cholesterol/protein ratio in LDL1 from the hypercholesterolaemic diabetic patients compared with controls. The LDL esterified/free cholesterol ratio was significantly greater in both LDL1 and LDL2 in the hypercholesterolaemic diabetic patients compared with the other two groups. There was a negative correlation between inhibition of cholesterol synthesis and the esterified/free cholesterol ratio of both LDL1 (r = 0.56, P < 0.002) and LDL2 (r = 0.63, P < 0.001). Cellular cholesterol of 41.0 +/- 0.3 microgram/mg cell protein in the hypercholesterolaemic diabetic patients was also significantly higher compared with values of 30.32 +/- 2.0 and 34.1 +/- 4.2 micrograms/mg cell protein for the normocholesterolaemic non-diabetic and diabetic groups. In vitro LDL esterification led to a decrease in LDL receptor-mediated binding and resulted in a 40% reduction in the ability of the LDL to suppress cholesterol synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Owens
D
D
Department of Clinical Medicine, Trinity College, Dublin, Ireland.
McBrinn
S
S
Collins
P
P
Johnson
A
A
Tomkin
G H
GH
D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood* / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D008875:Middle Aged; D011973:Receptors, LDL / Q000378:metabolism; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002784:Cholesterol; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014280:Triglycerides