ISSN:
1432-5233
Keywords:
Cellular cholesterol
;
Cholesterol synthesis
;
LDL binding
;
LDL composition
;
Type 2 diabetes
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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. LDL1 (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 μg/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 μg/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. The study demonstrates a relationship between the LDL esterified/free cholesterol ratio, LDL receptor binding and cellular cholesterol and may have implications for the understanding of hypercholesterolaemia in diabetes.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00569932
Permalink
