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Protein restriction and dexamethasone as a model of protein hypercatabolism in dogs: Effect of glutamine on leucine turnover

To determine (1) whether protein restriction, combined with glucocorticosteroid treatment, can be used as a hypercatabolic model and (2) if so, whether glutamine attenuates protein wasting in this model, the effects of protein restriction, dexamethasone, and glutamine on leucine metabolism were asse...

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Published in:Metabolism, clinical and experimental clinical and experimental, 2001-03, Vol.50 (3), p.293-298
Main Authors: Humbert, Bernard, Le Bacquer, Olivier, Nguyen, Patrick, Dumon, Henri, Darmaun, Dominique
Format: Article
Language:English
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Summary:To determine (1) whether protein restriction, combined with glucocorticosteroid treatment, can be used as a hypercatabolic model and (2) if so, whether glutamine attenuates protein wasting in this model, the effects of protein restriction, dexamethasone, and glutamine on leucine metabolism were assessed in dogs. A control group (n = 8) received a maintenance diet; another group (n = 8) received a protein-restricted diet either (1) alone; (2) along with a 7-day corticoid treatment; or (3) along with a 7-day corticoid treatment and a 7-hour intravenous (IV) glutamine infusion. The last day of each regimen, dogs underwent an IV isotope infusion in the fasting state, with a 3-hour NaH 13CO 3 infusion to assess CO 2 production, and immediately thereafter, a 3-hour 13C-leucine infusion to assess leucine appearance rate (Ra), oxidation (Ox), and nonoxidative leucine disposal (NOLD), expressed as μmol.kg −1.h −1. Protein restriction was associated with a 24% decline in leucine Ra (223 ± 16 v 298 ± 17; P < .01), an index of whole body proteolysis, and a 29% decline in NOLD (180 ± 15 v 223 ± 13; P < .01), an index of whole body protein synthesis. In the protein-restricted group, dexamethasone treatment was associated with a 32% increase in Ra, (295 ± 28 v 223 ± 16; P < .05), a 186% increase in Ox (120 ± 14 v 43 ± 4; P < .001), with no change in NOLD, when compared with the protein-restricted alone. After protein restriction + dexamethasone, glutamine infusion induced a 40% increase in plasma glutamine (1,090 ± 70 v 780 ± 29 μmol.L −1; P < .01), but failed to alter Ra, Ox, or NOLD. These results suggest that (1) in dogs, protein restriction combined with a 7-day course of dexamethasone results in alterations in leucine kinetics similar to those observed in stress-induced protein wasting in humans, and (2) in that model, a 7-hour IV glutamine infusion in the fasting state does not significantly attenuate protein wasting.
ISSN:0026-0495
1532-8600
DOI:10.1053/meta.2001.21018