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 act as initial acceptors of cellular cholesterol. Exogenous hyperinsulinaemia may not only decrease HDL cholesterol, but also plasma phospholipid transfer 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, pre beta-HDL in incubated plasma, plasma apolipoprotein (apo) AI, PLTP activity 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 decreased after 24 h of insulin (P<0.05 to P<0.01) compared to baseline and recovery, i.e. 1 week after insulin. Pre beta-HDL in incubated plasma did not significantly change. Cholesterol efflux to plasma from both groups decreased after insulin (P<0.05). Using plasma from healthy subjects, cholesterol efflux was correlated positively with HDL cholesterol, HDL phospholipids, 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 efflux was not significantly correlated with any of these parameters. In conclusion, 24-h moderate hyperinsulinaemia impairs the ability of plasma to promote cholesterol efflux from Fu5AH cells. It is suggested that, apart from HDL, plasma PLTP activity is a determinant of cholesterol efflux via stimulation of pre beta-HDL formation. Cellular cholesterol efflux to plasma from selected Type 2 diabetic patients is maintained, but the interaction of Fu5AH cells with HDL may be altered.
Dullaart
R P
RP
Department of Endocrinology, State University Hospital Groningen, PO Box 30 001, 9700 R.B. Groningen, The Netherlands. e.maris-smit@int.azg.nl
van Tol
A
A
D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001798:Blood Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage*; D008875:Middle Aged
D001798:Blood Proteins; D007328:Insulin; D002784:Cholesterol