Growth hormone administration increases glucose production by preventing the expected decrease in glycogenolysis seen with fasting in healthy volunteers

Twelve volunteers were fasted overnight and infused with [13C]glucose (ul) to measure glucose production (GP), gluconeogenesis, and by subtraction, glycogenolysis. Glucose production, gluconeogenesis, and glycogenolysis were measured after a 3-hour baseline infusion and two 4-hour infusions. The first 4 hours of the pituitary-pancreatic clamp study (PPCS) with replacement insulin, cortisol, and glucagon was without growth hormone (GH) administration. The second 4 hours of the PPCS was with high-dose GH administration. Six fasting volunteers acted as controls over the 11-hour study period. Overnight 12-hour fasting measurements of hormones, glucose, GP, gluconeogenesis, and glycogenolysis were similar in both groups. The PPCS had no significant effect on GP (2.43 ± 0.19 vs 2.07 ± 0.11 mg/kg per minute, PPCS vs controls, mean ± SEM). Glycogenolysis, as a percent of GP (43%-49%), was similar between PPCS and controls (43% ± 3% vs 49% ± 4%). High-dose GH for 4 hours increased GH (20.8 ± 3.8 vs 2.0 ± 0.9 ng/mL), blood glucose (127 ± 28 vs 86 ± 4 mg/dL, P < .05), GP (2.21 ± 0.21 vs 1.81 ± 0.12 mg/kg per minute, P < .05). The increase in GP was due to sustained glycogenolysis as compared to the observed fall in glycogenolysis seen with fasting alone (0.94 ± 0.21 vs 0.53 ± 0.07 mg/kg per minute, P < .05). Glycogenolysis, as a percent of GP, was significantly increased with high-dose GH (43 ± 5% vs 29 ± 3%, P < .05). High-dose GH had no effect on gluconeogenesis (1.26 ± 0.15 vs 1.29 ± 0.12 mg/kg per minute). High-dose GH prevents the fall in glycogenolysis observed with fasting alone.