Dose-response studies on the metabolic effects of a growth hormone pulse in humans

Abstract

Whereas the lipolytic and diabetogenic consequences of sustained growth hormone (GH) exposure are well described, the metabolic effects of a short-lived physiological GH pulse have only recently been reported. To assess the possible dose-response of such short-term bolus administration of GH, six healthy, male subjects were each studied thrice for 4 1 2 hours after an intravenous (IV) bolus of either 70, 140, or 350 μg GH, resulting in peak GH concentrations of 10, 15, and 34 μg/L. Observed results include: (1) Time- (but not dose-) dependent changes ( P < .05) in plasma glucose and an acute (from 10 minutes onward), persistent, 40% decrease in forearm glucose uptake. Total glucose turnover decreased steadily with time on all occasions. (2) Time- and dose-dependent increases ( P < .05) in the concentrations of circulating lipid intermediates, with an increase of 3-hydroxybutyrate (3-OHB) from a basal of 35 μmol/L to peak values of 108 ± 34 (70 μg), 176 ± 46 (140 μg), and 232 ± 51 μmol/L (350 μg), forearm uptake of 3-OHB changed in parallel. (3) Respiratory exchange ratio decreased ( P < .05) with increasing GH doses (indicating increased lipid and decreased glucose oxidation), and energy expenditure remained unaffected. (4) Concentrations of insulin, C-peptide, and glucagon were unchanged throughout all studies. We conclude that the stimulating effects of a modest GH bolus on circulating lipid intermediates and lipid oxidation are dose-dependent. This finding underlines the potential role of GH as a principal physiological regulator of fuel consumption in the maintenance of metabolic homeostasis.