|Thibault, Ronan - UNIVERSITE DE NANTES|
|Welch, Susan - NEMOURS CHILDRENS CLINIC|
|Mauras, Nelly - NEMOURS CHILDRENS CLINIC|
|Sager, Brenda - NEMOURS CHILDRENS CLINIC|
|Altomare, Astride - NEMOURS CHILDRENS CLINIC|
|Darmaun, Dominique - NEMOURS CHILDRENS CLINIC|
Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 26, 2007
Publication Date: February 1, 2008
Citation: Thibault, R., Welch, S., Mauras, N., Sager, B., Altomare, A., Haymond, M., Darmaun, D. 2008. Corticosteroids increase glutamine utilization in human splanchnic bed. American Journal of Physiology-Gastrointestinal and Liver Physiology. 294:G548-G553. Interpretive Summary: Glucocorticoid steroids are frequently used in disorders and diseases that have inflammation associated with them, such as inflammatory bowel disease and rheumatory arthritis. These compounds are associated with dramatic muscle wasting, and therefore understanding the mechanism of these losses and potential therapies to preserve muscle mass during steroid treatment is of vital importance. In this paper we examine the role of a key amino acid glutamine to determine whether the glucocorticoid steroids altered extraction of glutamine from the intestinal tract through the liver otherwise known as the splanchnic bed. Loss of this amino acid at this level would negatively impact its availability for protein metabolism. Glutamine is one of the amino acids that is thought to impact protein synthesis in a positive sense throughout the body. Using stable isotope tracers of glutamine being administered both orally and intravenously, we were able to determine the impacts of steroids on this process. We observed that glucocorticoid steroids increased the fraction of orally administered glutamine that was extracted by the splanchnic bed, and the absolute oxidation of glutamine was unaffected. We concluded that high dose glucocorticoid steroids increased splanchnic requirements for glutamine; however, the precise impact of this on overall whole body protein metabolism remains to be explored.
Technical Abstract: 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 en¬hanced glutamine de novo synthesis (medians +/- interquartiles, 412 +/- 61 vs. 280 +/- 190 umol•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.