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 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(13)CO3 infusion to assess CO2 production, and immediately thereafter, a 3-hour (13)C-leucine infusion to assess leucine appearance rate (Ra), oxidation (Ox), and nonoxidative leucine disposal (NOLD), expressed as micromol x kg(-1) x 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 micromol x 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.
Humbert
B
B
INSERM U.539, Centre de Recherche en Nutrition Humaine, Groupe Métabolisme, Hôtel-Dieu, Nantes, France.
Le Bacquer
O
O
Nguyen
P
P
Dumon
H
H
Darmaun
D
D
D000818:Animals; D003907:Dexamethasone; D004044:Dietary Proteins / Q000008:administration & dosage*; D004285:Dogs; D005938:Glucocorticoids; D005973:Glutamine / Q000494:pharmacology; D007275:Injections, Intravenous; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000209:etiology*; D010084:Oxidation-Reduction / Q000187:drug effects
D004044:Dietary Proteins; D005938:Glucocorticoids; D005973:Glutamine; D003907:Dexamethasone; D007930:Leucine