Insulin-dependent production of low-molecular-weight compounds that modify key enzymes in metabolism

The mechanism by which the metabolic effects of insulin are transmitted is yet to be resolved. Second messengers mediating the action of insulin have been proposed and recently an insulin-dependent, peptide-like, heat- and acid-stable substance (Mr approx. 1000-3000) released from plasma membranes has been described which regulates the activity of key enzymes such as pyruvate dehydrogenase by altering its state of phosphorylation. It has been suggested that this material is the elusive second messenger of insulin and its discovery, generation, properties, isolation and mode of action are reviewed.