Effects of glucocorticoids on glutamine metabolism in visceral organs

Souba, Wiley W.; Smith, Robert J.; Wilmore, Douglas W.

doi:10.1016/0026-0495(85)90211-2

Cited by 96 publications

(33 citation statements)

References 9 publications

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“…In several animal models of sepsis, increased rates of glutamine splanchnic extraction have been reported (27,40,41), but little is known in humans. In the present paper, the fate of splanchnic glutamine was examined by using the concomitant infusion of (18), the choice of tracer is unlikely to account for the observed changes in glutamine kinetics associated with prednisone.…”

Section: Discussionmentioning

confidence: 99%

“…A dramatic rise in the rate of glutamine uptake in splanchnic tissues has been documented in animal models of stress or after administration of glucocorticoids, which are believed to mediate some of the protein catabolic response to stress (2,27,38,40,42). It is well known that glucocorticoids mimic some of the alterations in amino acid metabolism observed in stressinduced protein wasting (5,24,35).…”

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confidence: 99%

“…By using this technique, ϳ50 to 75% of enterally administered glutamine undergoes first-pass extraction within the splanchnic bed, presumably by the gut and liver, in healthy humans (4, 17, 18, 34). Additionally, the major fate of splanchnic glutamine after enteral administration was oxidation, since 83% of the total tracer extracted was oxidized and only 10% was used for gluconeogenesis (17).A dramatic rise in the rate of glutamine uptake in splanchnic tissues has been documented in animal models of stress or after administration of glucocorticoids, which are believed to mediate some of the protein catabolic response to stress (2,27,38,40,42). It is well known that glucocorticoids mimic some of the alterations in amino acid metabolism observed in stressinduced protein wasting (5,24,35).…”

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Corticosteroids increase glutamine utilization in human splanchnic bed

Thibault

Welch²,

Mauras³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Thibault R, Welch S, Mauras N, Sager B, Altomare A, Haymond M, Darmaun D. Corticosteroids increase glutamine utilization in human splanchnic bed. Am J Physiol Gastrointest Liver Physiol 294: G548-G553, 2008. First published December 27, 2007 doi:10.1152/ajpgi.00461.2007.-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-[1-14 C]leucine and L-[ 2 H5]glutamine, along with q. 20 min oral sips of tracer doses of L-[1-13 C]glutamine in the fasting state, either 1) at baseline (control group; n ϭ 6) or 2) after a 6-day course of 0.8 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 prednisone (prednisone group; n ϭ 8). Leucine and glutamine appearance rates (Ra) were determined from plasma [1-14 C]ketoisocaproate and [ 2 H5]glutamine, respectively, and leucine and glutamine oxidation from breath 14 CO2 and 13 CO2, respectively. Splanchnic glutamine extraction was estimated by the fraction of orally administered [ 13 C]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 Ϯ interquartiles, 412 Ϯ 61 vs. 280 Ϯ 190 mol ⅐ kg Ϫ1 ⅐ h Ϫ1 , P ϭ 0.003); and 3) increased the fraction of orally administered glutamine undergoing extraction in the splanchnic territory (means Ϯ SE 64 Ϯ 6 vs. 42 Ϯ 12%, P Ͻ 0.05), without any change in the fraction of glutamine oxidized (means Ϯ SE, 75 Ϯ 4 vs. 77 Ϯ 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 GLUTAMINE PLAYS AN IMPORTANT role in the maintenance of intestinal function (39,43,46). Glutamine indeed is both a preferred fuel (9, 47) for enterocytes and a precursor for the intestinal synthesis of purines, pyrimidines (9), and glutathione (37), and it may regulate gut protein synthesis (21,30,32). In addition, glutamine is a major donor of carbon for gluconeogenesis (19). This explains why glutamine is extensively extracted in the splanchnic tissues in several animal species (39,47).In humans, the concomitant infusion of two tracers of glutamine (one infused intravenously, the other one enterally) can be used to assess the extraction of glutamine by the splanchnic bed. By using this technique, ϳ50 to 75% of enterally administered glutamine undergoes first-pass extraction within the splanchnic bed, presumably by the gut and liver, in healthy humans (4, 17, 18, 34). Additionally, the major fate of splanchnic glutamine after enteral administration was oxidation, ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Corticosteroids increase glutamine utilization in human splanchnic bed

Thibault

Welch²,

Mauras³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Part of the increased flux may represent increased interorgan exchange. In dogs, dexamethasone increases glutamine release by skeletal muscle and glutamine uptake by gut and kidney (16).…”

Section: Fetal Arterial Concentrations and Umbilical And Hepatic Upmentioning

confidence: 99%

“…In fasting dogs, dexamethasone has no detectable effect on glutamine uptake by the liver and increases hepatic alanine uptake (16). In rats, dexamethasone stimulates sodium-dependent glutamine uptake via system N transporters by cultured hepatocytes and by sinusoidal membrane vesicles isolated from liver homogenates (7).…”

Section: Fetal Arterial Concentrations and Umbilical And Hepatic Upmentioning

confidence: 99%