Effect of insulin on release of glucose and urea by isolated rat liver

Direct inhibitory effects of insulin on the release of glucose and urea from isolated livers of fasted and nonfasted rats have been established by use of an improved cyclic perfusion technique in situ. In livers of fasted animals the accumulation of perfusate glucose was small and, in the virtual absence of measurable glycogen, was presumed to be derived largely from protein. Insulin added to the perfusate caused an immediate partial inhibition of both glucose and urea release in amounts suggesting reduced gluconeogenesis. In livers of normal nonfasted rats, on the other hand, the output of glucose was far greater. Although insulin suppressed urea production as in the fasted rat liver, its inhibitory effect on glucose accumulation was severalfold larger. These facts pointed to the existence of a second, and quantitatively more important, action of insulin on hepatic glucose metabolism. With respect to its rapidity of onset, magnitude, and sensitivity to insulin this action compared favorably with glucose responses to insulin in isolated extrahepatic tissues.