Comparative studies on insulin-like growth factor II and insulin processing by vascular endothelial cells.
Processing of circulating polypeptide hormones by vascular endothelial cells may be critical to hormone transport from the vascular lumen to tissue sites of action. The comparative processing of insulin-like growth factor II (IGF II) and insulin by cultured bovine aortic endothelial cells was examined. These cells possess high-affinity receptors for IGF II and insulin, as shown by competitive-binding studies. At 37 degrees C, internalization determined by both resistance to an acid wash and electron microscopy was rapid with 50-70% of bound IGF II and insulin internalized at 60 min. Subsequently, between 70 and 75% of the internalized hormones were released from the cells within 60 min. Although most of both hormones were released intact, degradation of IGF II was greater than that of insulin by two- to threefold, as assessed by G-50 chromatography and trichloroacetic acid precipitability. Leupeptin, a specific lysosomal protease inhibitor, increased cell-associated 125I-labeled IGF II by 53.0 +/- 6.0% and decreased degradation by 55%; however, it was without effect on 125I-labeled insulin. Chloroquine and monensin, which act at the lysosomes and at other sites, increased both cell-associated IGF II and insulin and decreased the degradation of both hormones. The increases in cell-associated 125I-IGF II produced by chloroquine (42.0 +/- 7.4%) and monensin (78.3 +/- 8.5%) were quantitatively similar to the decreases in IGF II degradation caused by the agents; however, the increase in cell-associated insulin was approximately threefold greater than could be accounted for simply by decreased insulin degradation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001692:Biological Transport; D002417:Cattle; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D008954:Models, Biological; D008985:Monensin / Q000494:pharmacology; D011972:Receptor, Insulin / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*
D007328:Insulin; D007976:Leupeptins; D017451:Receptors, Somatomedin; D013002:Somatomedins; C008147:insulin, iodo-; D007335:Insulin-Like Growth Factor II; D002738:Chloroquine; D008985:Monensin; D011972:Receptor, Insulin; C032854:leupeptin