title: Effects of metalloendoprotease inhibitors on insulin binding, internalization and processing in adipocytes.
abstract: The effects of metalloendoprotease inhibitors on insulin binding, internalization, and processing were studied in isolated rat adipocytes. The metalloendoprotease inhibitor phosphoramidon caused a marked (threefold) increase in intracellular insulin accumulation without affecting surface binding. The dipeptide metalloendoprotease substrate analogues benzyloxycarbonyl-Gly-Phe-NH2 and benzyloxycarbonyl-Gly-Leu-NH2 caused similar large increases in intracellular insulin but also caused a doubling of cell surface bound insulin. The effect on surface binding was due to increased insulin receptor affinity as demonstrated by Scatchard analysis and the benzyloxycarbonyl-Gly-Phe NH2 induced inhibition of the dissociation of prebound insulin from the cell surface. These results suggest a role for endogenous metalloendoprotease-like enzymes in insulin processing by rat adipocytes.
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D010450:Endopeptidases; D006020:Glycopeptides / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D008666:Metalloendopeptidases; D008667:Metalloproteins; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D004151:Dipeptides; D006020:Glycopeptides; D007328:Insulin; D008667:Metalloproteins; D011480:Protease Inhibitors; D002738:Chloroquine; D011972:Receptor, Insulin; D010450:Endopeptidases; D008666:Metalloendopeptidases; C008890:phosphoramidon