Diabetogenic Effect of Some Cortin-Like Compounds

Abstract

Studies by Long and his coworkers demonstrated the diabetogenic effect of some of the steroid compounds occurring in the adrenal cortex. The effect of 11-desoxy-corticosterone acetate was found to be slight compared to that of corticosterone and 11-dehydro-corticosterone. Jensen and Grattan have reported that 11-desoxy-corticosterone acetate is much less effective in preventing insulin convulsions in mice than are corticosterone and 11-dehydro-cortico-sterone. In the following experiments partially depancreatized male rats having a body weight of approximately 280 g were used. The food intake of each animal was kept constant by administering the food by stomach tube in the manner described by Reinecke, Ball and Samuels. The test substances were dissolved in sesame oil and administered by subcutaneous injection twice daily. Each series of injections was continued for 4 days. The results are summarized in Table I. The compound 17-hydroxy-11-dehydro-corticosterone appears to be more potent than 11-desoxy-corticosterone in its diabetogenic effect. In the one test of 17-hydroxy-corticosterone the increase in the glycosuria was very marked, indicating that this substance is also very active. Jensen and Grattan have observed that the anti-insulin effect of 17-hydroxy-11-dehydro-corticosterone and 17-hydroxy-corticosterone is greater than the anti-insulin effect of 11-desoxy-corticosterone. The relative effects of the cortin-like compounds on carbohydrate metabolism parallel very closely their effects upon the capacity of adrenalectomized rats to work but differ from their relative maintenance activity. The author is grateful to Miss Dorothy Quinn for technical assistance; Dr. H. L. Mason of the Mayo Clinic, who supplied the sample of 17-hydroxy-11-dehydro-corticosterone acetate and 17-hydroxy-corticosterone; and Dr. E. Schwenk of the Schering Corporation, Bloomfield, New Jersey, who supplied the 11-desoxy-corticosterone acetate.