[Insulin-like effects of anti-insulin-receptor antibodies on cultured rat hepatocytes].
The effects of two anti-insulin-receptor antibodies (AIRA) on 125I-insulin binding, glycogenesis, amino-isobutyric acid (AIB) transport and insulin receptor down-regulation on cultured rat hepatocytes were examined. Two AIRA blocked insulin receptor dose-dependently and caused a decrease in available insulin receptor on hepatocytes. AIRA mimicked insulin action on glycogenesis both in short-term (2 h) and in long-term (24 h, 48 h) experiments, while AIRA did not mimic insulin action on AIB transport either in short-term (3,6 h) or in long-term (24 h) experiments. These results suggested that the post-receptor mechanism of insulin action is different between early effects (ex. glycogenesis) and late effects (ex. AIB transport) of insulin. On the other hand, insulin action on AIB transport in hepatocytes was shown to be mediated through insulin receptor, especially its high affinity binding sites, and this action was inhibited by AIRA in parallel with receptor blockade by AIRA. Furthermore, AIRA caused down-regulation of insulin receptor on hepatocytes in a dose-dependent and time-dependent fashion.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000502:physiology*; D001692:Biological Transport; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000276:immunology* / Q000502:physiology
D000596:Amino Acids; D001323:Autoantibodies; D007328:Insulin; D008112:Liver Glycogen; D011972:Receptor, Insulin