Growth Hormone-induced Diabetes and High Levels of Serum Insulin in Dogs

Abstract

Single injection of growth hormone (3 mg. per kilogram of body) in fasting dogs did not appreciably alter serum insulin and glucose concentrations within five hours. However, serum free fatty acids (FFA) decreased initially, then rose to two- and fourfold the initial at five and twenty-four hours. Following intravenous injection of glucose (1 gm. per kilogram of body) in the control period, serum insulin rose fourfold in 15 min. then regressed exponentially to the initial. Glucose/insulin remained unchanged during the two-hour test period, despite great alterations in the concentrations of glucose and insulin. Serum FFA decreased, then returned to or above the initial at one to two hours. Single injection of growth hormone did not alter these responses to the infusion of glucose. During the daily administration of 2 mg. of growth hormone per kilogram of body per day: (1) Mean serum insulin concentrations, in the postabsorptive periods, increased to two-, six- and eightfold the control value after one, two and four days, respectively, in six dogs, and thereafter the values remained high during seven to eleven days of observation in four dogs, while two developed resistance. (2) Serum insulin increased before an appreciable rise in serum glucose occurred. (3) Due to a greater rise in insulin than in glucose, the glucose/insulin ratio decreased. (4) After two days of injection the increase in serum insulin was most pronounced in those dogs that exhibited hyperglycemia and glycosuria. (5) Serum FFA increased greatly after one day of injection and remained high. During this growth hormone treatment, in one hour after injection of growth hormone with the ingestion of a meal, serum insulin rose, with lesser rise in glucose (further decrease in glucose/insulin), and fall in FFA. In the control period, however, no appreciable changes in serum insulin or glucose occurred following a meal. During daily growth hormone treatment, following glucose infusion: (1) Mean peak concentrations of serum insulin increased sevenfold in four days. (2) The rate of regression of serum insulin decreased. (3) Areas under the serum insulin curves increased up to tenfold the control value. (4) The mean rate of regression of serum glucose decreased, from the control value k — 4.28 per cent to —1.14 per cent after seven days. (5) The serum glucose/insulin ratio was unaltered, although the initial (fasting) values decreased. (6) The decline in serum FFA in 15 to 30 min. was more marked, but the levels remained above control. The changes in glucose/insulin indicate that growth hormone administration altered homeostatic control of pancreatic beta cells, such that at any given concentration of glucose in blood a greater rate of insulin secretion occurred. It is concluded that the “hyperinsulinemia” induced by the daily administration of growth hormone was associated with sustained increase in insulin secretion, and with augmentation of insulin secretion in response to a meal and to the infusion of glucose.