Insulin Degradation: Mechanisms, Products, and Significance*

EIGHT YEARS have passed since our previous review of insulin degradation in this journal (1). Much information has been obtained during this period, but the opening statement in that review remains true: Insulin degradation is a complex and incompletely understood process at present. The subcellular site, the cellular and enzymatic mechanisms, and especially the biological functions of insulin degradation all continue to be active and important areas of research. Although significant progress has been made, definitive conclusions are scarce. The purpose of this review is to examine the progress, draw some tentative conclusions, and advance some speculations. Work performed before 1980 will be discussed only briefly, and questions posed in the previous review will be answered, if possible, from the new information now available. New questions will be posed for future consideration. A. Insulin protease-insulin degrading enzyme The primary insulin degrading enzyme in tissues is a neutral thiol metalloproteinase which we have termed insulin protease (IP) (2).