The effect of insulin and glucagon on the insulin receptor of cultured hepatoma cells.

To elucidate the mechanism of glucagon-insulin (G-I) therapy, the effect of insulin and/or glucagon on the insulin receptor was studied in an experiment utilizing cultured cells (JTC-16) of rat ascites hepatoma. Insulin specific receptors were present on JTC-16 cells and were similar in nature to the receptors of primary culture rat hepatocytes. There were two kinds of insulin receptors. One had a high insulin affinity and the other had low insulin affinity. In the experiment involving addition of insulin the number of insulin receptors decreased after 24 hrs incubation in proportion to the increase in added insulin concentration. On the other hand, the number of insulin receptors increased with glucagon addition and the increase in proportion to the concentration of glucagon added. In the experiment involving simultaneous addition of insulin and glucagon, a 20% decrease in the number of receptors induced with 10(-9) M insulin was restored to the control level with simultaneous glucagon addition of the same concentration. The number of insulin receptors increased as the concentration of additive glucagon increased. These results show that simultaneous addition of insulin and glucagon inhibits the decrease in number of insulin receptors with insulin alone. These facts may obtain more potent action of insulin in G-I therapy via insulin receptor.