HYPOPHYSECTOMY OR ADRENALECTOMY OF RATS WITH INSULIN-DEPENDENT DIABETES-MELLITUS PARTIALLY RESTORES THEIR RESPONSIVENESS TO GROWTH-HORMONE

The studies reported herein were conducted to confirm that the pituita ry gland is involved in maintaining growth hormone (GH) resistance in rats with insulin-dependent diabetes mellitus (IDDM) and to determine whether the adrenocorticotropic hormone (ACTH)-adrenal cortical axis i s responsible. The rats were made diabetic by injecting streptozotocin (85 mg/kg body wt) IP once daily on two consecutive days. They were t hen injected with 15 IU insulin SC twice daily on two consecutive days to enable them to survive hypophysectomy or adrenalectomy. Intact non diabetic (NonDb), diabetic (Db), hypophysectomized diabetic (HxDb), an d adrenalectomized diabetic (AxDb) rats were injected twice daily with 50 mu g porcine (p) GH or with 0.9% saline for 2 weeks following the surgeries.Serum glucose levels of the saline-injected Db, HxDb, and Ax Db rats were significantly greater than those of the NonDb rats by 106 %, 65% and 49%, respectively. However, the levels in the HxDb and AxDb animals were significantly lower than those of the Db group by 20% an d 28%, respectively. Injections of pGH into NonDb rats increased serum glucose concentrations by 38%, over their saline-treated controls, an d by 29% in AxDb rats. This diabetogenic effect of GH was not seen in any other group. Administration of pGH to Db rats failed to increase b ody weight gain, tail growth, tibial epiphysial plate width, or serum IGF-I concentration over saline injected controls. By contrast, HxDb a nd AxDb rats injected with pGH showed significant increases in all fou r growth parameters. Total serum IGF-I concentrations in AxDb rats inj ected with pGH equaled those in NonDb controls. To determine whether t he lack of corticosterone (B) in the AxDb rats was responsible for the reduced hyperglycemia and restored responsiveness to pGH, AxDb rats w ere given B in their drinking water at 5 or 25 mu g/ml. Administration of B reduced the beneficial effects of adrenalectomy by restoring hyp erglycemia and growth impairment, and partially restored resistance to the pGH injections. These studies confirm that the pituitary contribu tes to diabetic growth impairment and show that the ACTH-adrenal corti cal axis is primarily responsible for the GH-resistant state that deve lops in rats with IDDM.