The Inhibitory Action of Insulin in the Early Chick Embryo

Abstract

ABSTRACT Insulin, in varying concentrations, has been applied to the chick embryo explanted by New’s technique after 24 hours incubation at stages 3–8 and cultured for 22–24 hours in vitro. It has been demonstrated that, in whatever manner insulin is applied to the embryo, its effects are most frequently manifest in the brain and neural tube. Somites are inhibited to a much lesser extent and heart, except with the higher doses, is unaffected. Application of either sodium pyruvate or nicotinamide with the insulin has very little protective action and larger doses of both these substances potentiate the inhibitory action of insulin. Diphosphopyridine nucleotide in the oxidized form given with the insulin provides complete protection, but the reduced form of DPN has no such effect. Previous work by Spratt and others on the metabolic characteristics of the early chick embryo, by Landauer on the teratogeni caction of insulin, and recent investigations (e.g. by Randle & Smith) are considered in the light of our findings. Like Duffey & Ebert (1957) we hesitate to accept Spratt’s (1950) hypothesis for the dependence of brain on oxidative mechanisms and the heart on glycolysis. We suggest, instead, that the heart, in contrast to the brain, can if necessary survive for a period of time under anaerobic conditions but, where possible, it makes full use of aerobic metabolic pathways. The complete protection afforded by DPN but not by DPNH leads us to believe that the site of action of insulin lies in the reoxidation of the pyridine nucleotides, i.e. in a hydrogen transport system.