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Am J Physiol Gastrointest Liver Physiol 294: G548-G553, 2008. First published December 27, 2007; doi:10.1152/ajpgi.00461.2007
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MUCOSAL BIOLOGY

Corticosteroids increase glutamine utilization in human splanchnic bed

Ronan Thibault,1,2,3 Susan Welch,4 Nelly Mauras,4 Brenda Sager,4 Astride Altomare,4 Morey Haymond,4,5 and Dominique Darmaun1,2,3,4

1Institut National de la Recherche Agronomique, Unité mixte de recherche 1280, Physiologie des Adaptations Nutritionnelles, Université de Nantes; 2Department of Gastroenterology and Nutritional Support, Centre Hospitalier Universitaire Hôtel Dieu; 3Centre de Recherche en Nutrition Humaine, Nantes, and Institut des Maladies de l'Appareil Digestif, Nantes, France; 4Nemours Children's Clinic, Jacksonville, Florida; and 5US Department of Agriculture Children's Nutrition Research Center at Baylor College of Medicine, Houston, Texas

Submitted 5 October 2007 ; accepted in final form 26 December 2007

Glutamine is the most abundant amino acid in the body and is extensively taken up in gut and liver in healthy humans. To determine whether glucocorticosteroids alter splanchnic glutamine metabolism, the effect of prednisone was assessed in healthy volunteers using isotope tracer methods. Two groups of healthy adults received 5-h intravenous infusions of L-[1-14C]leucine and L-[2H5]glutamine, along with q. 20 min oral sips of tracer doses of L-[1-13C]glutamine in the fasting state, either 1) at baseline (control group; n = 6) or 2) after a 6-day course of 0.8 mg·kg–1·day–1 prednisone (prednisone group; n = 8). Leucine and glutamine appearance rates (Ra) were determined from plasma [1-14C]ketoisocaproate and [2H5]glutamine, respectively, and leucine and glutamine oxidation from breath 14CO2 and 13CO2, respectively. Splanchnic glutamine extraction was estimated by the fraction of orally administered [13C]glutamine that failed to appear into systemic blood. Prednisone treatment 1) did not affect leucine Ra or leucine oxidation; 2) increased plasma glutamine Ra, mostly owing to enhanced glutamine de novo synthesis (medians ± interquartiles, 412 ± 61 vs. 280 ± 190 µmol·kg–1·h–1, P = 0.003); and 3) increased the fraction of orally administered glutamine undergoing extraction in the splanchnic territory (means ± SE 64 ± 6 vs. 42 ± 12%, P < 0.05), without any change in the fraction of glutamine oxidized (means ± SE, 75 ± 4 vs. 77 ± 4%, not significant). We conclude that high-dose glucocorticosteroids increase in splanchnic bed the glutamine requirements. The role of such changes in patients receiving chronic corticoid treatment for inflammatory diseases or suffering from severe illness remains to be determined.

nutrition; protein metabolism; stable isotopes; stress; gut



Address for reprint requests and other correspondence: D. Darmaun, INRA, UMR 1280 Physiologie des Adaptations Nutritionnelles, CHU Hôtel-Dieu, HNB1, 1 place Alexis Ricordeau, 44093 Nantes cedex 1, France (e-mail: ddarmaun{at}chu-nantes.fr)







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