Twenty four hour insulin infusion impairs the ability of plasma from healthy subjects and Type 2 diabetic patients to promote cellular cholesterol efflux

Removal of cholesterol from peripheral cells by high density lipoproteins ( HDL) is regarded as an important defence mechanism against atherosclerosis development. PLTP is involved in the generation of pre beta -HDL that can a ct as initial accepters of cellular cholesterol. Exogenous hyperinsulinaemi a may not only decrease HDL cholesterol, but also plasma phospholipid trans fer protein (PLTP) activity. The effect of 24-h insulin infusion (30 mU/kg/ h) on the ability of plasma to promote cholesterol efflux from Fu5AH cells was examined in eight healthy men and eight male Type 2 diabetic patients, matched for HDL cholesterol. Baseline HDL cholesterol and phospholipids, pr e beta -HDL in incubated plasma, plasma apolipoprotein (apo) AI, PLTP activ ity and cholesterol efflux to plasma were not different between the groups. In both groups, HDL lipids, as well as plasma apo AI and PLTP activity dec reased after 24 h of insulin (P < 0.05 to P < 0.01) compared to baseline an d recovery, i.e. 1 week after insulin. Pre beta -HDL in incubated plasma di d not significantly change. Cholesterol efflux to plasma from both groups d ecreased after insulin (P < 0.05). Using plasma from healthy subjects, chol esterol efflux was correlated positively with HDL cholesterol, HDL phosphol ipids, pre <beta>-HDL in incubated plasma, plasma apo AI and PLTP activity (P < 0.05 to P < 0.001). Using plasma from diabetic patients, cholesterol e fflux was not significantly correlated with any of these parameters. In con clusion, 24-h moderate hyperinsulinaemia impairs the ability of plasma to p romote cholesterol efflux from Fu5AH cells. It is suggested that, apart fro m HDL, plasma PLTP activity is a determinant of cholesterol efflux via stim ulation of pre beta -HDL formation. Cellular cholesterol efflux to plasma f rom selected Type 2 diabetic patients is maintained, but the interaction of Fu5AH cells with HDL may be altered. (C) 2001 Elsevier Science Ireland Ltd . All rights reserved.