Mediation of insulin-like growth factor actions by the insulin receptor in H-35 rat hepatoma cells.
We have used H-35 rat hepatoma cells to test whether the type II insulin-like growth factor (IGF) receptor mediates metabolic responses to IGF-II. On the basis of both affinity cross-linking experiments and competition binding experiments, H-35 cells display insulin and type II IGF receptors, but not type I IGF receptors. IGF-II and multiplication-stimulating activity (MSA; the rat homolog of IGF-II) stimulate tyrosine aminotransferase, amino acid transport, and glycogen synthase activities to the same magnitude as insulin. However, MSA and IGF-II stimulate these metabolic responses only at high concentrations, indicating that these peptides are acting through the insulin receptor. Incubation of H-35 cells with MSA also induces a state of unresponsiveness to the further actions of both MSA and insulin. There is no associated loss of either insulin or IGF-II binding, indicating that desensitization occurs at a postbinding step in hormone action. The high concentration of MSA necessary to induce desensitization is also consistent with MSA acting through the insulin receptor. We conclude that in H-35 cells, the insulin receptor, rather than the type II IGF receptor, mediates the metabolic responses stimulated by MSA and IGF-II as well as the MSA-induced desensitization to insulin and MSA action.
D000345:Affinity Labels; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000502:physiology*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000502:physiology*; D014444:Tyrosine Transaminase / Q000378:metabolism
D000345:Affinity Labels; D000596:Amino Acids; D007328:Insulin; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007335:Insulin-Like Growth Factor II; D006006:Glycogen Synthase; D014444:Tyrosine Transaminase; D011972:Receptor, Insulin