Effect of glutamine supplementation of the diet on tissue protein synthesis rate of glucocorticoid-treated rats

Bozá, J.; Turini, Marco; Moënnoz, Denis; Montigon, Franck; Vuichoud, Jacques; Gueissaz, Nathalie; Gremaud, G.; Pouteau, Etienne; Piguet-Welsch, Christelle; Finot, P. A.; Ballèvre, Olivier

doi:10.1016/s0899-9007(00)00505-0

Cited by 49 publications

(23 citation statements)

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“…Glucocorticosteroids indeed enhance glutamine de novo synthesis in rats (14), dogs (24), and humans (11). As already reported in hypercatabolic or corticosteroid-treated patients (5,16,26), the de novo synthesis of glutamine most likely occurs in peripheral tissues.…”

Section: Discussionsupporting

confidence: 56%

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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: Discussionsupporting

confidence: 56%

“…It is well known that glucocorticoids mimic some of the alterations in amino acid metabolism observed in stressinduced protein wasting (5,24,35). In humans, little is known about the effect of stress or glucocorticoids on glutamine uptake in splanchnic tissues.…”

mentioning

confidence: 99%

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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“…Two different ways of supplementing clinical nutrition products with glutamine, either with free glutamine or with a glutamine-rich protein source, were evaluated in hypercatabolic rats treated with glucocorticoids. Glutamine provided as dietary protein was extensively metabolized by the splanchnic tissues and did not influence peripheral glutamine status to the same extent as glutamine provided as the free amino (16). Glutamine depletion induced by inhibition of glutamine synthetase also led to a marked reduction of protein synthesis in cultured human enterocytes (17).…”

Section: Discussionmentioning

confidence: 98%

New insights in nutritional management and amino acid supplementation in urea cycle disorders

Scaglia

2010

Molecular Genetics and Metabolism

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Sodium phenylbutyrate is used in the pharmacological treatment of urea cycle disorders to create alternative pathways for nitrogen excretion. The primary metabolite, phenylacetate, conjugates glutamine in the liver and kidney to form phenylacetylglutamine that is readily excreted in the urine. Patients with urea cycle disorders taking sodium phenylbutyrate have a selective reduction in the plasma concentrations of branched chain amino acids despite adequate dietary protein intake. Moreover, this depletion is usually the harbinger of a metabolic crisis. Plasma branched chain amino acids and other essential amino acids were measured in control subjects, untreated ornithine transcarbamylase deficiency females, and treated patients with urea cycle disorders (ornithine transcarbamylase deficiency and argininosuccinate synthetase deficiency) in the absorptive state during the course of stable isotope studies. Branched chain amino acid levels were significantly lower in treated patients with urea cycle disorders when compared to untreated ornithine transcarbamylase deficiency females or control subjects. These results were replicated in control subjects who had low steady-state branched chain amino acid levels when treated with sodium phenylbutyrate. These studies suggested that alternative pathway therapy with sodium phenylbutyrate causes a substantial impact on the metabolism of branched chain amino acids in patients with urea cycle disorders, implying that better titration of protein restriction can be achieved with branched chain amino acid supplementation in these patients who are on alternative pathway therapy.

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“…[149][150][151][152] Several recent clinical trials have examined the impact of supplemental glutamine (14 g daily), in conjunction with arginine (14 g daily, a glutamine precursor) and HMB (3 g daily) in wasting disorders, including cancer. [153][154][155] In the cancer study, patients experiencing weight loss were randomized to receive, on a double-blind basis, either this supplementation program or an isonitrogenous blend of nonessential amino acids.…”

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confidence: 99%

Toward a Core Nutraceutical Program for Cancer Management

McCarty

Block

2006

Integr Cancer Ther

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As previously suggested, it may be feasible to impede tumorevoked angiogenesis with a nutraceutical program composed of glycine, fish oil, epigallocatechin-3-gallate, selenium, and silymarin, complemented by a low-fat vegan diet, exercise training, and, if feasible, a salicylate and the drug tetrathiomolybdate. It is now proposed that the scope of this program be expanded to address additional common needs of cancer patients: blocking the process of metastasis; boosting the cytotoxic capacity of innate immune defenses (natural killer [NK] cells); preventing cachexia, thromboembolism, and tumor-induced osteolysis; and maintaining optimal micronutrient status. Modified citrus pectin, a galectin-3 antagonist, has impressive antimetastatic potential. Mushroom β-glucans and probiotic lactobacilli can amplify NK activity via stimulatory effects on macrophages. Selenium, β-carotene, and glutamine can also increase the number and/or cytotoxic activity of NK cells. Cachectic loss of muscle mass can be opposed by fish oil, glutamine, and β-hydroxy-β-methylbutyrate. Fish oil, policosanol, and vitamin D may have potential for control of osteolysis. High-dose aspirin or salicylates, by preventing NF-κB activation, can be expected to aid prevention of metastasis and cachexia while down-regulating osteolysis, but their impacts on innate immune defenses will not be entirely favorable. A nutritional insurance formula crafted for the special needs of cancer patients can be included in this regimen. To minimize patient inconvenience, this complex core nutraceutical program could be configured as an oil product, a powder, and a capsule product, with the nutritional insurance formula provided in tablets. It would be of interest to test this program in nude mouse xenograft models.

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Effect of glutamine supplementation of the diet on tissue protein synthesis rate of glucocorticoid-treated rats

Cited by 49 publications

References 24 publications

Corticosteroids increase glutamine utilization in human splanchnic bed

Corticosteroids increase glutamine utilization in human splanchnic bed

New insights in nutritional management and amino acid supplementation in urea cycle disorders

Toward a Core Nutraceutical Program for Cancer Management

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