Role of Adenosine 3′,5′-Monophosphate in the Effects of Insulin and Anti-insulin Serum on Liver Metabolism

Abstract Injection of guinea pig anti-insulin serum into rats decreased the concentration of glycogen in the liver and increased the level of nonesterified fatty acid and glucose in the blood and the concentration of citrate in the heart. The uptake of glucose was reduced in hearts removed from antiserum-treated rats and perfused in vitro. Glucose production by perfused livers from rats treated with antiserum in vivo was increased as a result of accelerated glycogenolysis and gluconeogenesis. Urea production and K+ efflux were also increased. The rates of these processes could be reduced to or below control values by addition of insulin to the perfusion medium. Insulin added in vitro also decreased these processes and the loss of inorganic phosphate in livers from normal rats. Antiserum added to the medium perfusing normal hearts or livers was without effect except that it abolished the action of insulin. Administration of anti-insulin serum in vivo caused a progressive rise in the liver cyclic AMP concentration. Diabetes induced by alloxan also resulted in an increase in liver cyclic AMP, which was rapidly abolished by insulin treatment. Insulin added to the medium perfusing livers from normal or antiserum-treated rats caused a small decrease in liver cyclic AMP. Insulin antagonized the effects of epinephrine and glucagon on glucose output by the perfused liver and reduced the level of cyclic AMP in the presence of glucagon. The hypothesis is advanced that changes in cyclic AMP levels may be partly responsible for the alterations in liver metabolism caused by insulin and diabetes.