Stepwise Discovery of Insulin Effects on Amino Acid and Protein Metabolism

A clear effect of insulin deficiency and replacement on body/muscle mass was a landmark observation at the start of the insulin age. Since then, an enormous body of investigations has been produced on the pathophysiology of diabetes mellitus from a hormonal/metabolic point of view. Among them, the study of the effects of insulin on body growth and protein accretion occupies a central place and shows a stepwise, continuous, logical, and creative development. Using a metaphor, insulin may be viewed as a director orchestrating the music (i.e., the metabolic effects) played by the amino acids and proteins. As a hormone, insulin obviously does not provide either energy or substrates by itself. Rather, it tells cells how to produce and utilize them. Although the amino acids can be released and taken up by cells independently of insulin, the latter can powerfully modulate these movements. Insulin regulates (inhibits) protein degradation and, in some instances, stimulates protein synthesis. This review aims to provide a synthetic and historical view of the key steps taken from the discovery of insulin as an "anabolic hormone", to the in-depth analysis of its effects on amino acid metabolism and protein accretions, as well as of its interaction with nutrients.