The Effect of Growth Hormone and Cortisone O?; the Action of Bound Ixsulin*

There is abundant evidence that pituitary and adrenal cortical hormones influence insulin so as to produce marked alterations in its customary action on tissue metabolic patterns. There is little doubt that this reciprocal influence is manifest in many types of tissue and is particularly well established in the cases of liver and muscle. The injection of pituitary or adrenal hormones into normal hypophysectomized, or adreualectomized animals is also known to influence the action of insulin on the metabolism of various organs. Evidence is accumulating which strongly suggests that growth hormone is the pituitary principle which in the main is responsible for effects on carbohydrate metabolism. The possibility, however, that other pituitary principles may so act cannot be excluded. A variety of adrenocortical hormones are reported to influence different aspects of carbohydrate metabolism, but cortisone appears to be the most potent one. The rat diaphragm, first shown by Gemmill (1) to synthesize extra glycogen from glucose in t.he presence of insulin, has been extensively used to demonstrate interhormonal effects on glucose uptake or glycogen synthesis. Nelson (2) first showed that prior injection of pituitary extract diminished the subsequent synthesis of glycogen by .rat diaphragm in vitro. Park and Krahl (3) reported that injection of certain pituitary fractions depressed the glucose uptake in i&o by diaphragm from normal, hypophysectomized, and hypophysectomized-adrenalectomized rats, but that this depression was counteracted by insulin. Krahl, in a comprehensive but brief review of the recent literature (4), discussed extensive studies on the effects of pituitary and adrenal hormones on the action of insulin on glucose uptake by the rat diaphragm in vitro. Attempts to demonstrate hypersensitivity of the isolated diaphragm of the hypophysectomized rats to insulin have been reported. Early reports have been negative (Perlmutter and Greep (5), Krahl and Park (6), Stadie, Haugaard, Hills, and Marsh (7)). Borhstein and Nelson (8), using rats 14