Insulin receptor down-regulation, prevention at a post-receptor site.
Nicotinamide (50mM) prevented insulin-mediated down-regulation of insulin receptors in IM-9 lymphoblastoid cells. Half-maximum effectiveness was between 10 and 33mM. Nicotinamide did not influence insulin binding to the cells, cell viability, insulin degradation or protein synthesis. A variety of inhibitors of ADP-ribosylation reactions besides nicotinamide, most of them pyridine analogues, similarly prevented insulin-induced receptor loss. Spermine decreased the number of insulin receptors in IM-9 cells, but this effect was not inhibited by nicotinamide.
D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D006358:Hot Temperature; D007328:Insulin / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors; D011065:Poly(ADP-ribose) Polymerases; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D013096:Spermine / Q000494:pharmacology
D007328:Insulin; D009536:Niacinamide; D013096:Spermine; D003513:Cycloheximide; D011065:Poly(ADP-ribose) Polymerases; D011972:Receptor, Insulin; D009713:Nucleotidyltransferases