Are insulin receptors clinically significant?

Everything we know today about the functional defects underlying clinical diabetes mellitus was known before insulin receptors came along. Growth-onset (type I) diabetes stems from primary beta-cell failure; in these patients insulin sensitivity is normal, and the number of insulin receptors on target cells is normal. Adult-onset (type II) diabetes represents a combination of relative insulin deficiency (impaired early response to glycemic stimulus with subsequent hyperinsulinemia, at first) and peripheral insulin resistance, both of which engender 24 hr hyperinsulinemia that secondarily reduces insulin receptor concentrations. Concomitant obesity increases circulating hyperinsulinemia in moderately severe diabetes; however, excessive insulin levels wane as diabetes gets worse, and round-the-clock hypoinsulinemia supervenes. We still have to learn what fails to happen beyond the receptor concerning both glucose transport into the cell and insulin-mediated intracellular processes, but these postreceptor defects are undoubtedly related to deficient insulin secretion. In short, the hormone is more important than the receptor.