Effect of thyrotoxicosis on gluconeogenesis from alanine in the perfused rat liver

The influence and mechanism of action of T4 treatment on hepatic gluconeogenesis from alanine was studied in isolated rat livers. Conversion of alanine into glucose was increased markedly in livers of thyrotoxic rats compared to that in normal rats. Estimation of metabolic intermediates of the gluconeogenic pathway showed that T4 treatment produced forward cross-over between pyruvate and phosphoenolpyruvate, which suggests that this point is a control site. Alanine transport into the liver cells was apparently active since the alanine level was higher within the hepatocytes than in the extracellular space. Furthermore, T4 treatment stimulated the transport of alanine into the liver cells. alpha-Aminoisobutyric acid uptake was significantly higher by liver of thyrotoxic animals than of normal rats. The hepatic level of cAMP was also higher in experimental livers than control livers. These studies suggest that T4 stimulates hepatic gluconeogenesis from alanine and the underlying mechanism involves an increase in both the transport of amino acid into the liver cell and the conversion pyruvate to phosphoenolpyruvate.