Regulation of glucose uptake in muscle. V. The effect of growth hormone on glucose transport in the isolated, perfused rat heart.

The effects of growth hormone in the whole animal have been recently reviewed (1, 2). The following points are pertinent to the present work. The first injection of growth hormone into the hypophysectomized animal induces a hypoglycemic reaction similar to that which follows a small dose of insulin. This reaction is much less marked in a normal animal. After repeated injections of the hormone over several days in either the hypophysectomized or normal animal, the hypoglycemic reaction no longer occurs and a sustained hyperglycemia develops which varies greatly in intensity depending on the dosage and the species of animal involved. This “diabetic” phase of growth hormone activity is increased in severity by the concurrent administration of gluconeogenic adrenal steroids or by insulin deficiency. It is also characterized by an insensitivity to insulin. These effects of growth hormone on blood glucose can be accounted for in part by changes in peripheral glucose uptake. Earlier work (3) with the isolated rat diaphragm as an indicator of hormone effects in muscle gave the following findings. A few minutes after the first injection of growth hormone into hypophysectomized rats, glucose uptake by the diaphragm was stimulated. Addition of the hormone to the muscle in vitro had the same effect. This stimulation was not observed in diaphragms taken from hypophysectomized animals treated chronically with growth hormone or in the muscle from normal rats. In fact, repeated injection of growth hormone into either hypophysectomized or normal animals depressed glucose uptake by the excised diaphragm and this depression was augmented by the concurrent administration of adrenal cortical extracts. The muscle also showed an insensitivity to insulin. Although the above observations in vivo and in vitro seemed to fit well together, recent work suggested a reexamination of the findings. First, the studies of Altszuler et al. (4) have shown that the peripheral utilization of glucose by the hypophysectomized dog in the postabsorptive state is below normal and that utilization rises after repeated growth hormone injections. Second, the “cut” diaphragm is probably quite unreliable as an indicator of hormone effects on muscle. The transport step, which is usually rate-limiting for uptake, is bypassed to a large extent because of cut edges in the preparation. The recent studies of Kipnis (5), who measured penetration of the glucose analogue, Z-deoxyglucose, in the “cut” diaphragm from hypophysectomized rats, suggest that the high rate observed earlier