Insulin, Adenyl Cyclate, Ions, and the Heart

A bstract Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the carrier‐facilitated transport mechanism. For glucose, this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate‐limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production, and therefore maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably acting at the level of membrane‐bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin effects net and rapid potassium uptake by the heart cell and hyperpolarizes the cell, the change in the ratio of intracellular to extracellular activities of potassium is not the primary action of insulin. Rather, an insulin‐induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of adenyl cyclate are reduced by insulin in extracardiac tissues perhaps through inhibition of adenyl cyclase or stimulation of phosphodiesterase, but convincing evidence that this occurs in the heart is lacking. Insulin secretion is depressed in patients with heart disease in proportion to the reduction in cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate availability under these conditions. The multivalent actions of insulin on the heart cell are especially important in view of the resurgence of interest in glucose‐insulin‐potassium therapy for the treatment of clinical heart disease.