Attenuation of glycogenolytic action of activin A in intact rat liver.

Activin A stimulates glucose production by causing glycogenolysis in isolated hepatocytes. To determine the physiological significance of this effect, we examined the effect of activin A on glucose production in the perfused liver. Unlike the effect in isolated cells, activin A did not enhance glucose production nor did it cause radiocalcium efflux in the perfused liver. There was no effect of activin A in the liver perfused in the opposite direction. Although activin A did not promote glucose production, it was recovered from the hepatic vein in a bioactive form. When liver perfusion was performed in partially hepatectomized rats, activin A increased radiocalcium efflux. In isolated hepatocytes, activin A increased inositol phosphates, and the effect of activin A was attenuated by the plasma membrane fraction of hepatocytes. The inhibitory effect of the plasma membrane was abolished by digestion of the membrane with trypsin. These results indicate that the effect of activin A on glucose production is attenuated in the intact liver and that a protein factor(s) in plasma membrane may be involved in the inhibition.