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 × 10−8M). 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.

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