Insulin degradation by insulin target cells.

Recent findings illustrate the complexities associated with the interaction between insulin and its target cells. These results suggest that the processes involved in insulin action and those involved in insulin degradation may have certain steps in common. Both apparently begin when insulin binds to the insulin receptor. The next step is unknown but it ultimately leads to the internalization of the hormone before insulin dissociates from the cell surface. Furthermore, internalization appears to be a requirement for efficient degradation of insulin since the vast majority (perhaps all in certain cells) of the degrading activity is intracellular. Internalization may not be required to produce certain actions of the hormone, however, and the two processes may diverge at the point. It is not clear how insulin enters the target cell other than the process appears to be receptor-mediated. Also, further work is needed to more fully characterize the vesicles that contain internalized insulin. Finally, the actual location of insulin degradation and the enzyme(s) involved need further study, especially to clarify the relative contributions of lysosomes, cytosolic protease, and GIT to physiological insulin destruction. An understanding of the overall process of insulin degradation is required for a complete description of the physiologic disposition of the hormone at the target cell. Moreover, this system has subtle control mechanisms that may have important implications for the management of diabetes and other endocrine and metabolic disorders.