Endocrine Abstracts

Context and objective: During fasting growth hormone (GH) promotes lipolysis, attenuates glucose oxidation and preserves protein. Previous studies have primarily been conducted in GH deficient patients or during somatostatin-suppression of GH secretion. We aimed to study the impact of the fasting associated increase in GH without concomitant changes in other hormones, by the means of GH receptor (GHR) blockade.

Design: Ten healthy young men participated in a randomized, single-blinded, placebo-controlled, cross-over study with administration of 1) GHR blockade (pegvisomant, 15 mg s.c.) and 2) placebo (Saline, 1 ml) at 20.00 h at the beginning of a 36 h fast. All subjects were studied in the basal state (36–40 h of fasting) and at the end of a hyperinsulinemic euglycemic clamp (2½ h). Main outcome measures: palmitate flux, free fatty acids (FFA), ketone bodies, energy expenditure and oxidation rates, forearm uptake of FFA, insulin stimulated glucose-uptake, IGF-I (total and bioactive).

Results: GHR blockade significantly suppressed the levels and turnover of circulating FFA, ketogenesis, skeletal muscle uptake of FFA as well as lipid oxidation rate. This occurred in the presence of unaltered glucose and protein metabolism and without a detectable decline in IGF-I levels.

Conclusion: 1) Stimulation of lipolysis is the primary metabolic effect of GH during fasting. 2) Short-term fasting is a condition where FFA mobilization does not seem to result in either hepatic or peripheral insulin resistance. 3) GHR blockade by pegvisomant constitutes a promising tool for studying the physiological effects of GH on substrate metabolism.