The Mechanism of Regulation of the Blood Sugar by the Liver1

That the liver is essential for the maintenance of the level of blood sugar was demonstrated adequately by the early studies on the dehepatizeil animal. Because of the complexity of the problem, there has been much speculation concerning the mechanism responsible for the normal constancy of the blood sugar level and for the dextrose tolerance curve after the administration of sugar. From the studies of Soskin and his co-workers (1, 2, 3, 4, 5) on the dextrose tolerance curve under various experimental conditions, it would appear that whenever the blood sugar tends to rise above the normal level, the liver responds by diminishing its output of sugar to the blood. The stimulus which elicits this hepatic inhibitory response is the blood sugar itself, and the threshold of stimulation of the hepatic mechanism in a particular animal coincides with the level of blood sugar which that animal habitually maintains. It is suggested that this mechanism is chiefly responsible for the characteristic dextrose tolerance curve when sugar is administered to the normal animal. The influx of exogenous sugar into the blood stream raises the level of the blood sugar above the threshold of stimulation of the homeostatic mechanism. The liver promptly curtails the supply of sugar which it has been pouring into the blood. the liver. The exogenous sugar thus temporarily replaces the supply from Utilization and storage rapidly return the blood sugar toward its normal level, whereupon the liver resumes its secretion of sugar. This conception was based on indirect evidence. The facilities of the Institute of Experimental Medicine of The Mayo Clinic made it possible to obtain direct proof of the operation of this homeostatic mechanism of the . . liver. METHODS. From one to four months prior to our experiments, a twostage ligation of the posterior vena cava, just below the liver, was performed on the dogs to be used. This rerouting of the blood from the caudal