Inactivation of glucagon by tissues in vitro.

Abstract

A series of experiments are described in which glucagon was first incubated with a tissue preparation, then recovered by an acid-alcohol extraction, and, finally, assayed by rabbit liver slices. Failure to recover added glucagon was interpreted as loss by inactivation. Boiled tissue regularly yielded a complete recovery of added glucagon. Numerous tissues from the rabbit inactivated glucagon, as did dog and rat liver. Rabbit blood and plasma produced relatively little inactivation of glucagon. The inactivating system was studied further in rabbit liver homogenates. The effect was enzymic in nature, the enzyme system being present in the supernatant after subcellular fractionation. Inhibition of the system by p-chloromercuribenzoate and cupric ions suggests that sulphydryl groups may be necessary for activity of the enzyme system. Insulin and a crude ACTH preparation also inhibitied the inactivation of glucagon. The insulin effect was one of competitive inhibition. However, a comparison of the properties of the enzyme system in rat liver with published characteristics of insulinase revealed several differences between the two systems.