Processing of insulin-like growth factors I and II by capillary and large vessel endothelial cells.
Cultured endothelial cells from bovine capillaries and pulmonary arteries were incubated with highly purified [125I]insulin-like growth factor I ([125I]IGF-I), [125I]IGF-II, or [125I]insulin for periods up to 120 min, the cells were washed, and the cell-bound radioactivity was allowed to dissociate from the cells into fresh incubation medium. For insulin, 85-95% of the 125I dissociated from cells in 15 min, with 75% dissociating by 5 min. The 125I material released into the medium during the first 5 min of dissociation was entirely intact insulin, while the material released in the next 10 min was 80% intact insulin. For the [125I]IGFs, several differences were observed. First, after 5 min of dissociation, only 30-45% of the cell-bound 125I was released into the medium. For IGF-I, this rapidly dissociating material was entirely intact peptide, whereas for IGF-II, up to 55% of the dissociated radioactivity was degraded peptide. Second, during the next 10 min of dissociation, an additional 20% of the 125I was released from the cells. For IGF-I, this was 85% intact peptide; however, for IGF-II, this dissociated fraction contained as little as 25% intact peptide. Third, for both IGFs, after 15 min of dissociation, 40-65% of the initial cell-associated 125I remained within the endothelial cells; after the 15-min dissociation period, 95% of the remaining internalized 125I was intact IGF-I, whereas for IGF-II, the internalized 125I was 90% intact IGF-II after short periods of association (less than 15 min) and progressively decreased to 65% intact peptide after 60 min of association. We conclude that in addition to having separate surface receptors for insulin, IGF-I, and IGF-II, endothelial cells also process each hormone by distinct pathways.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001692:Biological Transport; D002196:Capillaries / Q000378:metabolism; D002417:Cattle; D002451:Cell Compartmentation; D004727:Endothelium / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007700:Kinetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*
D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II