STRUCTURAL AND COMPOSITIONAL MODIFICATIONS OF DIABETIC LOW-DENSITY LIPOPROTEINS INFLUENCE THEIR RECEPTOR-MEDIATED UPTAKE BY HEPATOCYTES

Dyslipoproteinaemia is an important risk factor for the development of atherosclerosis in noninsulin-dependent diabetes mellitus (NIDDM). Th is study shows that the uptake of low-density lipoproteins (LDLs) prep ared from the plasma of patients with NIDDM in cultured human hepatoma cells is largely reduced. In addition, diabetic LDL was less effectiv e in suppressing intracellular cholesterol synthesis. This is because of physicochemical and biochemical differences between lipoproteins fr om diabetic and from normal individuals. LDL from patients with NIDDM was abnormal with regard to charge, the degree of glycation, the lipid composition and the conformation of the apolipoprotein B receptor-bin ding domain. The diminished receptor-mediated uptake of apolipoprotein B-containing lipoproteins in diabetic individuals most probably leads to the accumulation of these lipoproteins in vivo and may be of great importance to the pathogenesis of atheroclerosis in these patients.