Cellular cholesterol regulation--a defect in the type 2 (non-insulin-dependent) diabetic patient in poor metabolic control.
This study investigates the relationship between Type 2 (non-insulin-dependent) diabetes mellitus and hypercholesterolaemia with regard to delivery of cholesterol to cells and regulation of endogenous cholesterol synthesis. The ability of LDL, from hypercholesterolaemic and Type 2 diabetic patients, to suppress cellular cholesterologenesis and to enhance mitogen-stimulated lymphocyte proliferation was compared. Cholesterol synthesis was estimated by measuring [14C]-acetate incorporation into cholesterol and lymphocyte proliferation was assessed by [3H]-thymidine incorporation into mitogen-stimulated normal lymphocytes. The results indicate that LDL from both Type 2 diabetic patients in poor metabolic control and hypercholesterolaemic patients was significantly less effective (p less than 0.001) than LDL from non-diabetic normocholesterolaemic subjects in suppressing cholesterol synthesis in lymphocytes. LDL from all hypercholesterolaemic patients enhanced lymphocyte proliferation to a greater extent than LDL from normocholesterolaemic subjects and this effect was significantly increased using LDL from Type 2 diabetic, hypercholesterolaemic patients. Both suppression of [14C]-acetate incorporation and enhancement of [3H]-thymidine uptake could be related to an increased esterified/free cholesterol ratio in the LDL particle. The fact that cholesterol synthesis and cell proliferation were markedly altered by the above changes in LDL composition suggests a mechanism for cellular cholesterol accumulation in the Type 2 diabetic patient, even in the absence of elevated serum cholesterol levels.
Owens
D
D
Department of Biochemistry, Royal College of Surgeons, Ireland.
Maher
V
V
Collins
P
P
Johnson
A
A
Tomkin
G
G
D001055:Apolipoproteins B / Q000097:blood; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D002788:Cholesterol Esters / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006031:Glycosylation; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000150:complications / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D002784:Cholesterol; D002788:Cholesterol Esters; D006442:Glycated Hemoglobin; D014280:Triglycerides