The anabolic actions of GH in GH-deficient adults and children are well documented. Replacement with GH in such individuals promotes protein synthesis and reduces irreversible loss of protein through oxidation. Although GH is known to be self-administered by athletes, its protein metabolic effects in this context are unknown. This study was designed to determine whether 4 wk of high dose recombinant human GH (r-hGH) administration altered whole body leucine kinetics in endurance-trained athletes at rest and during and after 30 min of exercise at 60% of maximal oxygen uptake. Eleven endurance-trained male athletes were studied, six randomized to receive r-hGH (0.067 mg/kg.d), and five to receive placebo. Whole body leucine turnover was measured at rest and during and after exercise, using a 5-h primed constant infusion of 1-[(13)C]leucine, from which rates of leucine appearance (an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (an index of protein synthesis) were estimated. Under resting conditions, r-hGH administration increased rate of leucine appearance and nonoxidative leucine disposal, and reduced leucine oxidation (P < 0.01). This effect was apparent after 1 wk, and was accentuated after 4 wk, of r-hGH administration (P < 0.05). During and after exercise, GH attenuated the exercise-induced increase in leucine oxidation (P < 0.05). There were no changes observed in placebo-treated subjects compared with the baseline study. We conclude that GH administration to endurance-trained male athletes has a net anabolic effect on whole body protein metabolism at rest and during and after exercise.

Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 µg · kg -1 · day -1 ) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemiceuglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1- 13C]leucine and [6-6-2 H 2 ]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26 ± 0.07 vs. 0.17 ± 0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (~67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37 ± 6 vs. 52 ± 10 µmol · kg -1 · min -1 , P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (~28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17 ± 0.03 vs. -0.10 ± 0.02, P < 0.01, and 0.25 ± 0.08 vs. 0.40 ± 0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulinstimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes. Diabetes 49:789-796, 2000 I GF-I shares a 40% sequence homology with human proinsulin and exhibits both insulin-like and anabolic effects (1,2). The availability of recombinant human IGF-I (rhIGF-I) has led to interest in the potential of this peptide in the treatment of a variety of disease states (3-7). Type 1 diabetes has received particular attention, because the relative portal insulin deficiency of this condition is thought to be responsible for the reduced circulating levels of IGF-I (8), which in turn, through decreased negative feedback, leads to increased secretion of growth hormone (GH) (9).Recent studies have demonstrated improved glycemic control in patients with types 1 and 2 diabetes after IGF-I treatment (10,11). IGF-I administration has also been shown to reduce the GH hypersecretion of adolescents and adults with type 1 diabetes (12,13). In those studies, the reductions in GH secretion were associated with decreased insulin requirements, without alteration in glycemic control, which indicates an increase in insulin sensitivity.In addition to disordered glucose metabolism, patients with t...

r-hGH in endurance-trained athletes increased lipolysis and fatty acid availability at rest and during and after exercise. r-hGH increased glucose production and uptake rates after exercise. The relevance of these effects for athletic performance is not known.