The uptake of glucose by the isolated diaphragm of normal and hypophysectomized rats.

It was reported (1) that the hexokinase reaction, glucose + adenosine triphosphate + glucose-&phosphate + adenosine diphosphate, in extracts of muscle from diabetic rats could be inhibited by adrenal cortical extract, while the hexokinase activity in extracts of normal muscle was inhibited by a combination of anterior pituitary and adrenal cortical extracts. The inhibition was in both cases relieved by insulin. In view of these findings, it became of interest to determine the extent to which the hexokinase reaction in muscle is controlled by insulin, adrenal cortical, and pituitary secretions. To this end, observations on the rate of glucose uptake by rat diaphragm were begun. This rate should be a measure of hexokinase activity in the muscle, since the hexokinase reaction is presumably the initial step in glucose utilization and is irreversible. In the initial series of experiments (2) it was found that the rate of glucose uptake by diaphragm from diabetic rats was depressed. This inhibition, appearing when insulin was lacking, could be counteracted, in part, by addition of insulin to the diaphragm in vitro or by adrenalectomy. Villee, Sinex, and Solomon (3), using C14-labeled glucose, have reported that glucose use, glycogen deposition, and carbon dioxide production were decreased in diaphragms from diabetic rats and increased in diaphragms from adrenalectomized rats. The present experiments were carried out to determine whether hexokinase activity was increased in diaphragms from rats lacking pituitary secretions and whether insulin would have any effect on the reaction under these circumstances.