Regulation of insulin responsiveness in rat hepatoma cells

Abstract

Insulin causes a 5 to 10-fold increase in the velocity of [alpha]-aminoisobutyric acid transport and a 2 to 3-fold increase in tyrosine aminotransferase activity in dexamethasone-treated hepatoma tissue culture cells. Maximal responses occur 2-4 hours after insulin addition but then decrease to control levels by 24 hours incubation. Medium conditioned by cells incubated with insulin for 24 hours retains sufficient biologically active insulin to produce an insulin response in fresh dexamethasone-treated cells. Readdition of insulin to insulin-treated cells, however, elicits no response, indicating that the cells are insensitive to the hormone. Incubation of such unresponsive cells in the absence of insulin results in recovery of responsiveness within 2 hours. These data suggest that exposure of rat hepatoma cells to insulin causes a complete but reversible loss of sensitivity to this hormone.