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

Abstract

Single injection of growth hormone (3 mg/kg of body) in fasting dogs did not appreciably alter serum insulin and glucose concentrations within 5 hr. However, serum free fatty acids (FFA) decreased initially, then rose to 2- and 4-fold the initial at 5 and 24 hr. Following intravenous injection of glucose (1g/kg of body) in the control period, serum insulin rose 4-fold in 15 min. then regressed exponentially to the initial. Glucose/insulin remained unchanged during the 2 hr. test period, despite great alterations in the concentrations of glucose and insulin. Serum FFA decreased, then returned to or above the initial at 1 to 2 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/kg of body/day (1) Mean serum insulin concentrations, in the postabsorp-tive periods, increased to 2-, 6- and 8-fold the control value after 1, 2 and 4 days, respectively, in 6 dogs, and thereafter the values remained high during 7 to 11 days of observation in 4 dogs, while 2 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 2 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 1 day of injection and remained high. During this growth hormone treatment, in 1 hr. 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 7-fold in 4 days. (2) The rate of regression of serum insulin decreased. (3) Areas under the serum insulin curves increased up to 10-fold the control value. (4) The mean rate of regression of serum glucose decreased, from the control value k - 4.28% to -1.14% after 7 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.