Adrenocorticotrophin in Relation to the Diabetogenic Activity of Growth Hormone Preparations

Abstract

The diabetogenic activity of preparations of growth hormone (GH) in intact cats was enhanced by the additional administration of preparations of adrenocorticotrophin (ACTH). High doses of ACTH alone were not diabetogenic under these conditions. The enhancing action of ACTH occasionally persisted for some time after cessation of ACTH injections, and was not associated with any marked lowering of the renal threshold for glucose.With a given ACTH preparation, the diabetogenic activity of purified GH was usually enhanced less than that of crude preparations.With a given GH preparation, the degree of enhancement differed with different ACTH preparations, and bore little relation to their effectiveness in the Sayers test. Experiments are in progress to test the possibility that these differences might merely reflect differences in the rate of absorption from the injection site.The experiments were performed in adult cats with an intact pancreas, under test conditions of which details have been given elsewhere [Reid, 1951 c]. Male or castratemale cats were usually employed, but anoestrous females were used in a few instances with results similar to those obtained in males. The cats were fed on a meat diet, the daily intake of which was kept almost constant. Any experiment which resulted in severe anorexia was considered invalid.Injections were given subcutaneously, and at different sites if two test substances were being administered concurrently. GH preparations were given once daily, and ACTH preparations usually three times per day (over 8 hr). Each period of treatment with GH was terminated when a glucose excretion exceeding 5 g in 24 hr was obtained, and the next test was commenced only when the urine had been free of sugar for at least 6 days. Ketonuria was not observed in any of the experiments reported below.