When insulin or any peptide hormone binds to its receptor on the surface of a target cell, it initiates a series of biochemical steps that ultimately lead to the characteristic action of the hormone. The strength of the signal generated by the hormone depends equally on the hormone concentration, the receptor concentration, and the receptor affinity. Not only do hormone concentrations change rapidly and widely in vivo but so do receptor concentration and affinity. In hormone resistant states, any step in the biochemical pathway of hormone action at the target cell may be involved. Studies of insulin receptors in people indicate that the insulin receptor is altered in many common disorders such as obesity and diabetes, as well as in rare disorders such as extreme insulin resistance due to circulating antibodies directed at the insulin receptor itself. By responding to both intracellular and extracellular events, the insulin receptor is, therefore, a major site for the regulation of target cell responsiveness in vivo.
(Arch Intern Med 137:474-481, 1977)