Diabetogenic Effect of Some Cortin-Like Compounds

Abstract

Studies by Long and his coworkers 1 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 2 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 3 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. 4 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 5 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 6 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.