Processing of cell-bound insulin by capillary and macrovascular endothelial cells in culture.
The processing of cell-bound insulin was determined in endothelial cells cultured from three large blood vessels (human umbilical vein, bovine pulmonary artery, and bovine aorta) and one microvascular source (bovine fat capillaries). Cells were exposed to monoiodinated TyrA14-insulin, the rates of dissociation of cell-bound TyrA14-insulin determined, and cell alteration of insulin assessed by gel filtration and high-performance liquid chromatography analysis. We found that 1) overall degradation rates of insulin are low for all cultured endothelial cells, 2) cell-bound insulin is rapidly processed to a nonreceptor compartment and then rapidly dissociated from all cells, primarily as biologically intact insulin, and 3) degradation of cell-bound insulin, although relatively low, does occur in endothelial cells with the least degradation by capillary cells. The presence of specific surface receptors for insulin on endothelial cells coupled with rapid cellular processing of intact insulin is consistent with a potential role for endothelial cells in either the transport of intact insulin out of the bloodstream or as a regional storage site for intact hormone.
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism*; D013997:Time Factors; D014471:Umbilical Veins / Q000378:metabolism*
D007328:Insulin; C029491:insulin, 3-iodo-Tyr(A14)-; D002738:Chloroquine