Regulation of insulin receptors in cultured human fibroblasts

The ability of insulin to regulate its own receptor was investigated in cultured human fibroblasts. Physiological insulin concentrations led to a loss of insulin receptors, and this process was dependent on cellular energy and ongoing protein synthesis. The insulin concentration primarily affected the rate of receptor loss rather than the eventual cellular receptor concentration. Studies of receptor regeneration revealed that the absolute rate of insertion of new or recycled receptors into the plasma membrane was constant and independent of the amount of proceeding receptor loss or the time over which receptor loss occurred. These results are compatible with the concept that insulin-induced receptor loss in cultured human fibroblasts is a self-limited process mediated by an endocytotic internalization pathway which is dependent on new protein synthesis. Receptor regeneration is a distinct cellular process dependent on ongoing protein synthesis and does not imply represent the absence of ongoing receptor loss.