Effects of Glutamine and Recombinant Human Growth Hormone on Protein Metabolism in Prepubertal Children with Cystic Fibrosis

Abstract

To determine whether recombinant human GH (rhGH) and glutamine (GLN), alone or in combination, have a protein anabolic effect and whether rhGH alters GLN kinetics in cystic fibrosis (CF), nine 9.6 +/- 0.5-yr-old children with CF who were either undernourished (weight/height, <50th percentile) or short (height, <5th percentile) received 2-h infusions of [(13)C]bicarbonate (to assess CO(2) production), followed by 4-h infusions of [(13)C]leucine and [(15)N]GLN, on 4 separate days in the postabsorptive state: 1) at baseline, and after a 4-wk treatment with 2) oral GLN (0.7 g/kg.d), 3) rhGH (0.3 mg/kg.wk), and 4) GLN and rhGH combined (GLN and rhGH regimens were in randomized order). No significant effect of GLN on leucine kinetics was detectable. In contrast, rhGH induced a 32% reduction in leucine oxidation and a 13% stimulation of nonoxidative leucine disposal, an index of protein synthesis (P < 0.05), with no change in proteolysis or GLN kinetics. The combined GLN plus rhGH regimen had similar effects as rhGH alone. We conclude that in children with CF, 1) oral GLN may not promote protein gain in the fasting state; and 2) a short course of rhGH has a potent anabolic effect that is mediated by stimulation of protein synthesis and does not affect GLN kinetics.

Recombinant Human Growth Hormone in the Treatment of Patients With Cystic Fibrosis

“…3, Of the 10 trials, 8 trials compared rhGH to no treatment, [14][15][16][17][23][24][25][26] 1 trial used a placebo control, 3 and 1 trial compared rhGH alone to either glutamine or the combination of glutamine and rhGH. 20 A crossover design was used in 2 trials, 16,20 whereas the others used a parallel study design. 3,14,15,17,[23][24][25][26] Only 1 trial was doubleblinded.…”

“…3,14,15,17,[23][24][25][26] Only 1 trial was doubleblinded. 3 Four trials received funding from foundations or government, [14][15][16]26 8 trials received funding from indus-try, 3,14,15,17,20,23,25,26 and a funding source was not reported for 2 of the trials. 24,30 Four of the aforementioned trials received both industry and foundation funding to conduct their studies.…”

“…24,30 Four of the aforementioned trials received both industry and foundation funding to conduct their studies. [14][15][16]20,23 In 1 of the 10 trials patients were treated with rhGH for 4 weeks, 20 whereas in the other trials patients were treated for 6 months to 1 year. 3,[14][15][16][17][23][24][25][26] Chronological age of the patients was up to 23 years, but 6 trials specifically evaluated prepubertal children, [14][15][16]20,[23][24][25][26] and 1 study evaluated only pubertal adolescents.…”

Beneficial effect of recombinant human growth hormone on the intestinal mucosa barrier of septic rats

“…Both animal and human studies have demonstrated that recombinant human growth hormone (rhGH) can enhance protein synthesis, promote tissue recovery, stimulate intestinal epithelial growth, etc. (3)(4)(5). However, the mechanism of the protective effect of rhGH on the intestinal mucosa barrier is not understood.…”

Incorporação protéica de L[1-13C] leucina em ratos desnutridos:efeita da suplementação oral de glutamina.

“…Sugere-se, inclusive, que a glutamina diminui a atrofia da mucosa intestinal, induzida por diferentes agressões e patologias em modelos animais (WINDMUELLER & SPAETH, 1978) e melhora a função de absorção intestinal (TREMEL et al, 1994). Porém estes efeitos anabólicos, aparentemente, utilizando metodologia mais adequada, não têm sido ratificados em humanos e cães (MARCHINI et al, 1999, DARMAUN et al, 2004. O corpo humano abrange perto de 9 kg de proteína, principalmente na forma de proteína muscular.…”