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

Divisions of Endocrinology (D.D., V.H., S.W., N.M.) and Pulmonology (D.S.), Nemours Children’s Clinic, Jacksonville, Florida 32207; and Institut National de la Santé et de la Recherche Médicale, Unité 539, Centre de Recherche en Nutrition Humaine (D.D.), 44093 Nantes, France

Address all correspondence and requests for reprints to: Dr. Dominique Darmaun, Nemours Children’s Clinic, Endocrine Research, 807 Children’s Way, Jacksonville, Florida 32207. E-mail: ddarmaun{at}nemours.org.

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 [¹³C]bicarbonate (to assess CO₂ production), followed by 4-h infusions of [¹³C]leucine and [¹⁵N]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.

This work was supported in part by grants from the Genentech Foundation for Growth and Development (Charlottesville, VA) and the Nemours Research Programs (Jacksonville, FL).

Abbreviations: B_GLN, Glutamine release from protein breakdown; BIA, bioelectrical impedance analysis; CF, cystic fibrosis; DEXA, dual energy x-ray absorptiometry; Excr_13CO2, ¹³CO₂ excretion; %FM, percentage of fat mass; FR_CO2, fractional recovery of ¹³CO₂ in breath; GLN, glutamine; KIC, -ketoisocaproate; LBM, lean body mass; NOLD, nonoxidative leucine disposal; Ox_Leu, leucine oxidation; Ra, appearance rate; rhGH, recombinant human GH.

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