Cellular Cholesterol Regulation--a Defect in the Type 2 (non-insulin-dependent) Diabetic Patient in Poor Metabolic Control

Overview

Journal Diabetologia

Specialty Endocrinology

Date 1990 Feb 1

PMID 2328848

Citations 4

Authors

D Owens

V Maher

P Collins

A Johnson

G Tomkin

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Conway Memorial Lecture 2002. The dyslipidaemia of diabetes: lessons in the pathogenesis of atherosclerosis.

Tomkin G Ir J Med Sci. 2003; 171(4):220-4.

PMID: 12647914 DOI: 10.1007/BF03170286.

Regulation of low-density lipoprotein particle size distribution in NIDDM and coronary disease: importance of serum triglycerides.

Lahdenpera S, Syvanne M, Kahri J, Taskinen M Diabetologia. 1996; 39(4):453-61.

PMID: 8777995 DOI: 10.1007/BF00400677.

The effect of low density lipoprotein composition on the regulation of cellular cholesterol synthesis: a comparison in diabetic and non-diabetic subjects.

Owens D, McBrinn S, Collins P, Johnson A, Tomkin G Acta Diabetol. 1993; 30(4):214-9.

PMID: 8180413 DOI: 10.1007/BF00569932.

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment.

Gylling H, Miettinen T Diabetologia. 1994; 37(8):773-80.

PMID: 7988779 DOI: 10.1007/BF00404334.

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