Insulin: fundamental mechanism of action and the heart.
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 at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. 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 cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
D000596:Amino Acids / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism
D000596:Amino Acids; D002352:Carrier Proteins; D007328:Insulin; D000242:Cyclic AMP; D005947:Glucose; D011188:Potassium; D002118:Calcium