Interrelationship between amino acid and carbohydrate metabolism--with special reference to hormonal regulation

Abstract

The changes of the activities of serine dehydratase (SDH) and glucokinase were examined in order to evaluate dietary and hormonal effects on the metabolism of amino acids and carbohydrate.1) In the livers of alloxan-diabetic rats, about a sixfold increase of SDH was observed, and this increase was diminished to the normal level by the injection of protamine zinc insulin. The increase was inhibited approximately 75% by an administration of actinomycin S. Adrenalectomized rats showed no increase of SDH for 48 hours after the injection of alloxan monohydrate, although a gradual increase was observed 3 to 4 days later.On the basis of these facts, adrenalectomized rats treated with alloxan monohydrate at zero time, were given three injections of 5 mg of hydrocortisone acetate at 15, 24 and 40 hours and then sacrificed at 45 hours. SDH was enhanced about fivefold, whereas no increase was found without the alloxan treatment. In normal rats, daily administration of 15mg of hydrocortisone acetate for 3 days produced only a 1.7 fold increase. No increase of SDH was observed in rats which were hypophysectomized either before or after the injection of alloxan monohydrate. An injection of somatotrophic hormone proved to be ineffective on SDH in the hypophysectomized alloxan-diabetic rats.2) The activity of glucokinase decreased to one seventh of normal level in the liver of alloxan-diabetic rats. The activity returned to normal level by the injection of protamine zinc insulin. Adrenalectomy showed no inhibitory effect on the decrease of glucokinase in the alloxan-diabetic rats. Hydrocortisone acetate could not affect the activity of glucokinase in the liver of adrenalectomized alloxan-diabetic rats.3) No increase of SDH was observed after starvation for 3 days. In the rats fed with high protein diet, SDH increased to the same level as in the alloxan-diabetic rats.4) As indicated by the activity of SDH, the conversion of serine to pyruvate increases in the liver of alloxan-diabetic rats, and pyruvate is synthesized to glucose through the pathway of the activated gluconeogenesis. The utilization of glucose is inhibited in the diabetic rats as shown by the decreased activity of glucokinase.5) The response of SDH to hydrocortisone as evidenced by the elevation of SDH activity in adrenalectomized alloxan-diabetic rats supports the view that insulin counteracts the effect of hydrocortisone on SDH. Of special interest in this connection, there are similar reciprocal changes between the activites of SDH and glucokinase in the livers of alloxan-diabetic and high protein-fed rats compared with normal rats.It is a problem to be solved whether a dietary stress might regulate the flow rate of metabolites via hormonal control.