title: Lipoprotein-induced insulin resistance in aortic endothelium.
abstract: 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.
mesh_terms: D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007333:Insulin Resistance; D007700:Kinetics; D008074:Lipoproteins / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000494:pharmacology; D008315:Malondialdehyde / Q000494:pharmacology
chemical_list: D000621:Aminoisobutyric Acids; D007328:Insulin; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D008315:Malondialdehyde; D002784:Cholesterol