The Effect of Insulin upon Urea Formation, Carbohydrate Synthesis, and Respiration of Liver of Normal and Diabetic Animals*

The severely diabetic subject has an excessive protein metabolism which returns to normal when sufficient carbohydrate utilization is reestablished. The current hypothesis to explain this is that restoration of the ability to oxidize carbohydrate spares protein, and the metabolism returns to normal. An alternative hypothesis, namely that insulin has a direct specific effect on protein metabolism, is also a possibility. Recently, Bach and Holmes (1937) found evidence for it on the basis of experiments with slices of normal fasted rat liver equilibrated in bicarbonate buffer. They found, both with no added substrate and with dl-alanine, that insulin, when added to the medium, partially inhibited urea formation and carbohydrate synthesis. They concluded that a function of insulin is the suppression of glyconeogenesis by the inhibition of oxidative deamination of glycogenic amino acids. The importance of this hypothesis concerning a specific action of insulin upon protein metabolism led us to test it extensively. Our experiments indicate that a possible role of insulin in protein metabolism is the regulation of the deamination by the liver of the d isomers (so called unnatural isomers) of glycogenic and nonglycogenic amino acids.