Lipoprotein-induced insulin resistance in aortic endothelium

An in vitro model system employing cultured, adult, bovine aortic endothelial cells was used to study the mechanism of insulin stimulation of aminoisobutyric acid (AIB) uptake and the effects of low-density lipoprotein (LDL), malondialdehyde-altered LDL (MDA-LDL), and B-migrating very-low-density lipoprotein (B-VLDL) on this process. The insulin response was maximal after treatment with insulin for 2 h (at a concentration of 5 X 10(-8) M). Insulin increased the Vmax but not the KM of the uptake response. Increasing the cell cholesterol content by a 3-day incubation with malondialdehyde-altered low-density lipoprotein or B-very-low-density lipoprotein, but not low-density lipoprotein, resulted in resistance to the action of insulin. This resistance was not due to a decreased number of insulin receptors or to a decreased receptor affinity. Additionally, the resistance was not abolished by increasing the time of insulin exposure or the concentration of insulin to which the cells were exposed. These findings suggest a postreceptor defect either at the membrane level or intracellularly.