Insulin-induced receptor regulation in cultured Zajdela rat hepatoma cells and relationship to the stimulation of glycogen synthesis.
Insulin receptors were measured in cultured Zajdela rat hepatoma cells (ZHC cells), a stable cell line which presents differentiated hepatic functions. The number of sites was 50,000/cell at 2 C, and the dissociation constant for high affinity binding was 1.6 x 10(-10) M. Down-regulation of receptors occurred rapidly when cells were treated with insulin; this process was related to ambient insulin concentrations and led to a decrease in the number of insulin receptors from 50,000 to 30,000/cell. Cycloheximide prevented part of this regulation. When down-regulated cells were incubated in standard medium devoid of insulin, the number of receptor sites gradually increased and attained control values within 7 h; cyclohexamide inhibited this process. Insulin markedly enhanced glycogen synthesis in ZHC cells, with an ED50 of 1.0 x 10(-9) M, leading to an increase in the total cell glycogen content. In addition, the predicted righthand shift of the dose-response curve was observed for insulin-treated cells. These findings provide evidence of insulin-induced receptor regulation in cultured ZHC cells which is related to the biological effect of the hormone on glycogen synthesis.
D000818:Animals; D002460:Cell Line; D003470:Culture Media; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008112:Liver Glycogen / Q000096:biosynthesis*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D003470:Culture Media; D007328:Insulin; D008112:Liver Glycogen; D011972:Receptor, Insulin; D005947:Glucose