Muscle Glutamine Concentration Research Articles

Changes in Skeletal Muscle Protein Metabolism Signaling Induced by Glutamine Supplementation and Exercise.

To evaluate the effects of resistance exercise training (RET) and/or glutamine supplementation (GS) on signaling protein synthesis in adult rat skeletal muscles. The following groups were studied: (1) control, no exercise (C); (2) exercise, hypertrophy resistance exercise training protocol (T); (3) no exercise, supplemented with glutamine (G); and (4) exercise and supplemented with glutamine (GT). The rats performed hypertrophic training, climbing a vertical ladder with a height of 1.1 m at an 80° incline relative to the horizontal with extra weights tied to their tails. The RET was performed three days a week for five weeks. Each training session consisted of six ladder climbs. The extra weight load was progressively increased for each animal during each training session. The G groups received daily L-glutamine by gavage (one g per kilogram of body weight per day) for five weeks. The C group received the same volume of water during the same period. The rats were euthanized, and the extensor digitorum longus (EDL) muscles from both hind limbs were removed and immediately weighed. Glutamine and glutamate concentrations were measured, and histological, signaling protein contents, and mRNA expression analyses were performed. Supplementation with free L-glutamine increased the glutamine concentration in the EDL muscle in the C group. The glutamate concentration was augmented in the EDL muscles from T rats. The EDL muscle mass did not change, but a significant rise was reported in the cross-sectional area (CSA) of the fibers in the three experimental groups. The levels of the phosphorylated proteins (pAkt/Akt, pp70S6K/p70S6K, p4E-BP1/4E-BP1, and pS6/S6 ratios) were significantly increased in EDL muscles of G rats, and the activation of p4E-BP1 was present in T rats. The fiber CSAs of the EDL muscles in T, G, and GT rats were increased compared to the C group. These changes were accompanied by a reduction in the 26 proteasome activity of EDL muscles from T rats. Five weeks of GS and/or RET induced muscle hypertrophy, as indicated by the increased CSAs of the EDL muscle fibers. The increase in CSA was mediated via the upregulated phosphorylation of Akt, 4E-BP1, p70S6k, and S6 in G animals and 4E-BP1 in T animals. In the EDL muscles from T animals, a decrease in proteasome activity, favoring a further increase in the CSA of the muscle fibers, was reported.

Controlled trial of whole body protein synthesis and plasma amino acid concentrations in yearling horses fed graded amounts of lysine

Lysine has been reported as the first limiting amino acid in typical equine diets. Indicator amino acid oxidation (IAAO) has become the standard method for determining amino acid requirements in other species, but prior to this study, it has not been used to determine equine requirements. The aim of this study was to evaluate whole body protein synthesis and plasma and muscle amino acid concentrations in response to graded levels of lysine intake in yearling horses. Six Thoroughbred colts (358 ± 5 kg) were fed each of six treatment lysine intakes ranging from 76 to 136 mg/kg body weight/day. Blood samples were taken before and 90 min after the morning concentrate meal. Gluteal muscle biopsies were taken ~100 min after the morning concentrate meal. The next day, whole body phenylalanine kinetics were determined using a 2 h primed, constant infusion of [13C] sodium bicarbonate followed by a 6 h primed, constant infusion of [1-13C] phenylalanine. Plasma lysine concentrations increased linearly (P < 0.05) at both the 0 and 90 min time points with increasing lysine intakes. Free muscle asparagine, aspartate, arginine, glutamine, lysine, taurine and tryptophan concentrations responded quadratically to lysine intake (P < 0.05). Phenylalanine kinetics did not differ between treatment intakes (P > 0.10). A broken line analysis of lysine intake and phenylalanine oxidation failed to yield a breakpoint from which to determine a lysine requirement. These diets may have been limiting in an amino acid other than lysine, underscoring the lack of data concerning amino acid requirements and bioavailability data in the horse.

The Effects of Glutamine Loading on Strength Performance

Glutamine is purported to have beneficial effects on muscle glycogen resynthesis and immune system responses post exercise. Following a physiological stress, glutamine supplementation may sustain muscle glutamine content, increase muscle protein synthesis and attenuate protein catabolism. A resistance training stimulus often results in an elevated protein turnover and may induce glycogen depletion, therefore glutamine supplementation may augment strength training responses. PURPOSE: The purpose of this study is to determine the effects of 7 days of glutamine loading on muscular strength performance. METHODS: In a double-blind crossover study, 16 participants (mean body mass [BM] 72 ± 5.6 kg, height 178 ± 12.2 cm, age 23.5 ±2.4 yrs) performed trials of resistance training after randomly being assigned to either a seven day loading phase of glutamine supplementation (G) of 0.3 g·kg of glutamine per day mixed with calorie free fruit juice or a placebo (P) of only juice. A warm-up on both the Nautilus Leg Press (LP) and Nautilus Chest Press (CP) of 10-12 reps at 20% BM were required prior to each trial. Trials consisted of 2 sets of LP at 150% BM and 2 sets of CP at 50% BM at a 3-1-3 movement cadence to momentary muscular fatigue with 1 minute rest between sets. Blood lactate was obtained after the second set. The aforementioned trials were conducted as a baseline (B) at pre-workout and in a fatigued condition (F) immediately following a resistance training workout. A seven day washout period was required between crossover aspects of the study. Statistical analysis by ANOVA at P< .05 were applied to these data. RESULTS: The repetitions performed were significantly greater in the following trials: Chest Press; Set 1 (7.75 ± 2.8 vs 6.56 ± 2.0), Set 2 (6.88 ± 2.9 vs 5.69 ± 2.2), Leg Press; Set 1 B (18.63 ± 9.3 vs 15.81 ± 6.7), Set 2 B (14.94 ± 8.5 vs 12.56 ± 6.5), and F Set 2 (11.19 ± 5.7 vs 9.63 ± 5.5) for G vs P conditions, respectively. CONCLUSION: A seven day regiment of glutamine supplementation permits an increase in the total work load (repetitions), which may, in part, be attributed to enhanced glycogen resynthesis. Because of the acute nature of this study, it is unknown if continued glutamine supplementation in combination with resistance training would augment the normal progression of muscular strength or hypertrophy.

Oral supplementations with free and dipeptide forms of l-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins

Sepsis is a leading cause of death in intensive care units worldwide. Low availability of glutamine contributes to the catabolic state of sepsis. l-Glutamine supplementation has antioxidant properties and modulates the expression of heat shock proteins (HSPs). This study investigated the effects of oral supplementation with l-glutamine plus l-alanine (GLN+ALA), both in the free form and l-alanyl-l-glutamine dipeptide (DIP), on glutamine-glutathione (GSH) axis and HSPs expression in endotoxemic mice. B6.129F2/J mice were subjected to endotoxemia (lipopolysaccharides from Escherichia coli, 5 mg.kg−1, LPS group) and orally supplemented for 48 h with either l-glutamine (1 g.kg−1) plusl-alanine (0.61 g.kg−1) (GLN+ALA-LPS group) or 1.49 g.kg−1 of DIP (DIP-LPS group). Endotoxemia reduced plasma and muscle glutamine concentrations [relative to CTRL group] which were restored in both GLN+ALA-LPS and DIP-LPS groups (P<.05). In supplemented groups were re-established GSH content and intracellular redox status (GSSG/GSH ratio) in circulating erythrocytes and muscle. Thiobarbituric acid reactive substance was 4-fold in LPS treated mice relative to the untreated CTRL group, and plasma TNF-α and IL-1β levels were attenuated by the supplements. Heat shock proteins 27, 70 and 90 (protein and mRNA) were elevated in the LPS group and were returned to basal levels (relative to CTRL group) in both GLN+ALA-LPS and DIP-LPS groups. Supplementations to endotoxemic mice resulted in up-regulation of GSH reductase, GSH peroxidase and glutamate cysteine ligase mRNA expression in muscle. In conclusion, oral supplementations with GLN+ALA or DIP are effective in reversing the conditions of LPS-induced deleterious impact on glutamine-GSH axis in mice under endotoxemia.

Oral free and dipeptide forms of glutamine supplementation attenuate oxidative stress and inflammation induced by endotoxemia

ObjectiveThe aim of the present study was to determine the effects of oral supplementation with l-glutamine plus l-alanine (GLN+ALA), both in the free form and l-alanyl-l-glutamine dipeptide (DIP) in endotoxemic mice. MethodsB6.129 F2/J mice were subjected to endotoxemia (Escherichia coli lipopolysaccharide [LPS], 5 mg/kg, LPS group) and orally supplemented for 48 h with either l-glutamine (1 g/kg) plus l-alanine (0.61 g/kg) (GLN+ALA-LPS group) or 1.49 g/kg DIP (DIP-LPS group). Plasma glutamine, cytokines, and lymphocyte proliferation were measured. Liver and skeletal muscle glutamine, glutathione (GSH), oxidized GSH (GSSG), tissue lipoperoxidation (TBARS), and nuclear factor (NF)-κB–interleukin-1 receptor-associated kinase 1 (IRAK1)–Myeloid differentiation primary response gene 88 pathway also were determined. ResultsEndotoxemia depleted plasma (by 71%), muscle (by 44%), and liver (by 49%) glutamine concentrations (relative to the control group), which were restored in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Supplemented groups reestablished GSH content, intracellular redox status (GSSG/GSH ratio), and TBARS concentration in muscle and liver (P < 0.05). T- and B-lymphocyte proliferation increased in supplemented groups compared with controls and LPS group (P < 0.05). Tumor necrosis factor-α, interleukin (IL)-6, IL-1 β, and IL-10 increased in LPS group but were attenuated by the supplements (P < 0.05). Endotoxemic mice exhibited higher muscle gene expression of components of the NF-κB pathway, with the phosphorylation of IκB kinase-α/β. These returned to basal levels (relative to the control group) in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Higher mRNA of IRAK1 and MyD88 were observed in muscle of LPS group compared with the control and supplemented groups (P < 0.05). ConclusionOral supplementations with GLN+ALA or DIP are effective in attenuating oxidative stress and the proinflammatory responses induced by endotoxemia in mice.

Glutamine and glutamate supplementation raise milk glutamine concentrations in lactating gilts

Glutamine is the most abundant amino acid in milk, and lactation is associated with increased glutamine utilization both for milk synthesis and as a fuel for the enlarged small intestine. A number of recent studies have indicated that lactation is accompanied by a mild catabolic state in which skeletal muscle proteins are degraded to provide amino acids that are used to synthesize additional glutamine. In this study we tested the hypothesis that supplemental L-glutamine or the commercially available glutamine supplement Aminogut (2.5% by weight mixed into daily feed) provided to gilts from 30 days prior to parturition until 21 days post-parturition would prevent a decrease in skeletal muscle glutamine while increasing the glutamine content of the milk. Muscle glutamine content decreased (P < 0.05) in control animals during lactation but this was prevented by supplementation with either L-glutamine or Aminogut. In this study, neither lactation nor supplementation had any effect on plasma glutamine or glutamate content. Free glutamine, and the total glutamine plus glutamate concentrations in milk from the control and the Aminogut group rose (P < 0.05) during the first 7 days of lactation, with milk concentrations in the L-glutamine supplemented group showing a similar trend (P = 0.053). Milk glutamate remained constant between day 7 and 21 of lactation in the control and L-glutamine supplemented groups, but by day 21 of lactation the free glutamine, glutamate, and glutamine plus glutamate concentrations in milk from Aminogut-treated gilts were higher than those of control gilts. Thus dietary glutamine supplementation can alleviate the fall in intramuscular glutamine content during lactation in gilts, and may alleviate some of the catabolic effects of lactation. Furthermore, the increased milk glutamine content in the supplemented gilts may provide optimum nutrition for piglet development.

Acute hyperammonemia activates branched-chain amino acid catabolism and decreases their extracellular concentrations: different sensitivity of red and white muscle

Hyperammonemia is considered to be the main cause of decreased levels of the branched-chain amino acids (BCAA), valine, leucine, and isoleucine, in liver cirrhosis. In this study we investigated whether the decrease in BCAA is caused by the direct effect of ammonia on BCAA metabolism and the effect of ammonia on BCAA and protein metabolism in different types of skeletal muscle. M. soleus (SOL, slow-twitch, red muscle) and m. extensor digitorum longus (EDL, fast-twitch, white muscle) of white rat were isolated and incubated in a medium with or without 500 μM ammonia. We measured the exchange of amino acids between the muscle and the medium, amino acid concentrations in the muscle, release of branched-chain keto acids (BCKA), leucine oxidation, total and myofibrillar proteolysis, and protein synthesis. Hyperammonemia inhibited the BCAA release (81% in SOL and 60% in EDL vs. controls), increased the release of BCKA (133% in SOL and 161% in EDL vs. controls) and glutamine (138% in SOL and 145% in EDL vs. controls), and increased the leucine oxidation in EDL (174% of controls). Ammonia also induced a significant increase in glutamine concentration in skeletal muscle. The effect of ammonia on intracellular BCAA concentration, protein synthesis and on total and myofibrillar proteolysis was insignificant. The data indicates that hyperammonemia directly affects the BCAA metabolism in skeletal muscle which results in decreased levels of BCAA in the extracellular fluid. The effect is associated with activated synthesis of glutamine, increased BCAA oxidation, decreased release of BCAA, and enhanced release of BCKA. These metabolic changes are not directly associated with marked changes in protein turnover. The effect of ammonia is more pronounced in muscles with high content of white fibres.

EFFECT OF EXERCISE ON GLUTAMINE SYNTHESIS AND TRANSPORT IN SKELETAL MUSCLE FROM RATS

1. Reductions in plasma glutamine are observed after prolonged exercise. Three hypotheses can explain such a decrease: (i) high demand by the liver and kidney; (ii) impaired release from muscles; and (iii) decreased synthesis in skeletal muscle. The present study investigated the effects of exercise on glutamine synthesis and transport in rat skeletal muscle. 2. Rats were divided into three groups: (i) sedentary (SED; n = 12); (ii) rats killed 1 h after the last exercise bout (EX-1; n = 15); and (iii) rats killed 24 h after the last exercise bout (EX-24; n = 15). Rats in the trained groups swam 1 h/day, 5 days/week for 6 weeks with a load equivalent to 5.5% of their bodyweight. 3. Plasma glutamine and insulin were lower and corticosterone was higher in EX-1 compared with SED rats (P < 0.05 and P < 0.01, respectively). Twenty-four hours after exercise (EX-24), plasma glutamine was restored to levels seen in SED rats, whereas insulin levels were higher (P < 0.001) and corticosterone levels were lower (P < 0.01) than in EX-1. In the soleus, ammonia levels were lower in EX-1 than in SED rats (P < 0.001). After 24 h, glutamine, glutamate and ammonia levels were lower in EX-24 than in SED and EX-1 rats (P < 0.001). Soleus glutamine synthetase (GS) activity was increased in EX-1 and was decreased in EX-24 compared with SED rats (both P < 0.001). 4. The decrease in plasma glutamine concentration in EX-1 is not mediated by GS or glutamine transport in skeletal muscle. However, 24 h after exercise, lower GS may contribute to the decrease in glutamine concentration in muscle.

Nitrogen metabolism and branchial osmoregulatory acclimation in the juvenile marble goby, Oxyeleotris marmorata, exposed to seawater

The marble goby, Oxyeleotris marmorata, considered a freshwater fish, was able to hypoosmoregulate successfully during 14 days of acclimation to seawater (30‰) following 6 days of progressive increase in salinity. In seawater, there were slight perturbations in plasma osmolality and ionic concentrations, and significant increases in contents of some free amino acids, which presumably acted as osmolytes, in tissues. The muscle glutamine content increased significantly during seawater acclimation, and the activity and the protein abundance of glutamine synthetase increased significantly in the liver of fish exposed to seawater for 14 days. Exposure to seawater for 14 days also resulted in branchial osmoregulatory acclimation. There were significant increases in the activity and the protein abundance of gill Na +/K +-ATPase, and protein abundance of gill Na +:K +:2Cl − cotransporter (NKCC). Immunofluorescence microscopy of branchial Na +/K +-ATPase-immunoreactive cells revealed that exposure to seawater led to increases in protein expression of apical cystic fibrosis transmembrane receptor-like chloride channel and basolateral NKCC. Overall, our results indicate that juvenile marble goby can acclimate to brackish water and subsequently to seawater, and prompt future studies on the effects of salinity on its growth and development which may have important application to the Asian marble goby aquaculture industry.

Changes in glutamine metabolism indicate a mild catabolic state in the transition mare1

Glutamine is the most abundant free alpha-AA in the mammalian body, and large amounts of glutamine are extracted by both the fetus during pregnancy and the mammary gland during lactation. The work presented here addressed the hypothesis that there would be major changes in glutamine metabolism in the mare during the transition period, the time between late gestation, parturition, and early lactation. Eight foals were born to Standardbred mares provided with energy and protein at 10% above NRC recommendations, and foals remained with mares for 6 mo. During lactation, lean body mass decreased by 1.5% (P < 0.05), whereas fat mass was unchanged throughout gestation and lactation. There was a sharp increase in the concentration of most plasma metabolites and hormones after birth, which was due in part to hemoconcentration because of fluid shifts at parturition. Plasma glutamine concentration, however, was maintained at greater concentrations for up to 2 wk postpartum but then began to decrease, reaching a nadir at approximately 6 wk of lactation. Skeletal muscle glutamine content did not change, but glutamine synthetase expression was decreased at the end of lactation (P < 0.05). Free glutamine was highly abundant in milk early in lactation, but the concentration decreased by more than 50% after 3 mo of lactation and paralleled the decrease in plasma glutamine concentration. Thus, lactation represents a mild catabolic state for the mare in which decreased glutamine concentrations may compromise the availability of glutamine to other tissues such as the intestines and the immune system.

Changes in glutamine metabolism indicate a mild catabolic state in the transition mare

Glutamine is the most abundant free alpha-AA in the mammalian body, and large amounts of glutamine are extracted by both the fetus during pregnancy and the mammary gland during lactation. The work presented here addressed the hypothesis that there would be major changes in glutamine metabolism in the mare during the transition period, the time between late gestation, parturition, and early lactation. Eight foals were born to Standardbred mares provided with energy and protein at 10% above NRC recommendations, and foals remained with mares for 6 mo. During lactation, lean body mass decreased by 1.5% (P < 0.05), whereas fat mass was unchanged throughout gestation and lactation. There was a sharp increase in the concentration of most plasma metabolites and hormones after birth, which was due in part to hemoconcentration because of fluid shifts at parturition. Plasma glutamine concentration, however, was maintained at greater concentrations for up to 2 wk postpartum but then began to decrease, reaching a nadir at approximately 6 wk of lactation. Skeletal muscle glutamine content did not change, but glutamine synthetase expression was decreased at the end of lactation (P < 0.05). Free glutamine was highly abundant in milk early in lactation, but the concentration decreased by more than 50% after 3 mo of lactation and paralleled the decrease in plasma glutamine concentration. Thus, lactation represents a mild catabolic state for the mare in which decreased glutamine concentrations may compromise the availability of glutamine to other tissues such as the intestines and the immune system.

Dietary Glutamine Supplementation Increases the Activity of Peritoneal Macrophages and Hemopoiesis in Early-Weaned Mice Inoculated with Mycobacteriumbovis Bacillus Calmette-Guérin

Infants who are breast-fed have been shown to have a lower incidence of certain infectious diseases compared with formula-fed infants. Glutamine is one of the most abundant amino acids found in maternal milk and it is essential for the function of immune system cells such as macrophages. The purpose of this study was to investigate the effect of glutamine supplementation on the function of peritoneal macrophages and on hemopoiesis in early-weaned mice inoculated with Mycobacterium bovis bacillus Calmette-Guérin (BCG). Mice were weaned at 14 d of age and distributed to 2 groups and fed either a glutamine-free diet (n = 16) or a glutamine-supplemented diet (+Gln) (n = 16). Both diets were isonitrogenous (with addition of a mixture of nonessential amino acids) and isocaloric. At d 21, 2 subgroups of mice (n = 16) were intraperitoneally injected with BCG and all mice were killed at d 28. Plasma, muscle and liver glutamine concentrations and muscle glutamine synthetase activity were not affected by diet or inoculation with BCG. The +Gln diet led to increased leukocyte and lymphocyte counts in the peripheral blood (P < 0.05) and granulocyte and lymphocyte counts in the bone marrow and spleen (P < 0.05). The +Gln diet increased spreading and adhesion capacities, hydrogen peroxide, nitric oxide, and tumor necrosis factor-α (TNF α) syntheses and the phagocytic and fungicidal activity of peritoneal macrophages (P < 0.05). The interaction between the +Gln diet and BCG inoculation increased the area under the curve of interleukin (IL)-1 β and TNF α syntheses (P < 0.05). In conclusion, the intake of glutamine increases the function of peritoneal macrophages and hemopoiesis in early-weaned and BCG-inoculated mice. These data have important implications for the design of breast milk substitutes for human infants.

Does Long‐Term Intermittent Treatment With Glutamine Improve the Well‐being of Fed and Fasted Very Old Rats?

Glutamine is known to have a specific role in very old rats (>25 months of age). For this reason, we have orally supplemented female rats with glutamine (20% of diet protein) intermittently. The treatment started before animals became very old and lasted 5 months. Very old rats were studied in fed state or after 5-day fasting after the last glutamine cure. The aim of this study was to determine whether this in vivo pretreatment improves the well-being of very old rats (muscle sarcopenia decrease, gut integrity improvement, decrease of the known up-regulated glutamine synthetase observed regardless of nutrition state). Protein turnover was measured in epitrochlearis muscle, whereas glutamine synthetase (GS) activities were assessed in tibialis anterior muscle from fed and 5-days-fasted female Wistar adult (6 months) and very old (27 months) rats, pretreated or not with glutamine. Furthermore, gut was dissected and weighed. Long-term treatment with glutamine had positive effects on very old rats: (1) it prevented the loss of body weight, but, (2) it did not prevent the inevitable sarcopenia regardless of nutrition state, and (3) it maintained the gut mass. Surprisingly, the muscle up-regulated GS activity observed in fed and fasted very old rats was only decreased in the fed state when rats were supplemented, without change in plasma and muscle glutamine concentrations. Long-term treatment with glutamine started before advanced age had essentially a beneficial role on the gut. It may play a role in maintaining intestine integrity and intestinal immune function. Further investigations would be warranted to explore these mechanisms.

Simultaneous Infusion of Glutamine and Branched‐Chain Amino Acids (BCAA) to Septic Rats Does Not Have More Favorable Effect on Protein Synthesis in Muscle, Liver, and Small Intestine Than Separate Infusions

Glutamine and branched-chain amino acids (BCAA; valine, leucine, and isoleucine) are used as nutrition supplements in the treatment of proteocatabolic illness. We hypothesized that simultaneous administration of BCAA and glutamine affects protein metabolism more significantly than separate administration. In the present study, we evaluated their effect on protein synthesis in skeletal muscle, liver, and jejunum of septic rats. Twenty-four hours after induction of sepsis by subcutaneous injection of turpentine, the rats were infused for 6 hours with 5 mL of 1.75% glutamine, 1.75% BCAA, 1.75% glutamine+BCAA, or saline solution. The control group consisted of intact rats infused with saline. Protein synthesis was measured at the end of infusion by a "flooding method" with [3,4,5-(3)H]phenylalanine. In turpentine-treated animals, we observed a decrease in glutamine concentration in blood plasma and skeletal muscle, a decrease in BCAA concentration in liver and jejunum, and a decrease in protein synthesis in all tissues. Glutamine or glutamine+BCAA infusion increased glutamine concentration in plasma and muscle and stimulated protein synthesis in the liver. The BCAA infusion enhanced concentrations of BCAA in plasma and tissues, but the effect of BCAA on protein synthesis was insignificant. Synergistic effect of simultaneous infusion of glutamine and BCAA on protein synthesis was not observed. We conclude that glutamine infusion to rats with septic injury may significantly improve impaired protein synthesis in the liver and that there is no synergistic effect of glutamine and BCAA infusion on protein synthesis in skeletal muscle, liver, and jejunum.

Aspects of Protein and Amino Acid Metabolism in a Model of Severe Glutamine Deficiency in Sepsis

Background/Aims: Growth hormone (GH) could have the potential to improve protein metabolism in sepsis but glutamine deficiency has been reported after GH treatment. The aim was to investigate the effects of glutamine deficiency in sepsis with and without GH treatment on protein and amino acid metabolism. Methods: Cecal ligation and puncture (CLP) was used as a model of sepsis. Serious glutamine deficiency was induced by administration of glutamine synthetase inhibitor, methionine sulfoximine (MSO). Young Wistar rats were divided into 5 groups: control; CLP; CLP+MSO; CLP+GH, and CLP+MSO+GH. Parameters of protein metabolism were measured on incubated soleus and extensor digitorum longus muscles: [1-¹⁴C]leucine was used to estimate protein synthesis and leucine oxidation, tyrosine release was used to evaluate protein breakdown. Amino acid concentrations in plasma, skeletal muscle and incubation media were measured by HPLC. Results/Conclusions: A reduced muscle glutamine concentration after MSO treatment is not associated with changes in the rates of protein synthesis or breakdown. MSO treatment decreased glutamine release from skeletal muscle and plasma glutamine concentration. Severe glutamine deficiency in GH-treated septic rats resulted in increased release of branched-chain amino acids from skeletal muscle.

Effect of alanyl-glutamine supplementation on plasma and tissue glutamine concentrations in rats submitted to exhaustive exercise

Objective We investigated the effect of supplementation with L-glutamine and L-alanyl-L-glutamine (DIP) on the plasma and tissue glutamine concentrations of exercise-trained rats immediately and 3 hours after a single exercise session until exhaustion. Methods Thirty-six male rats were divided into six groups, and then subdivided into groups submitted only to the exhaustion test: control (CON-EXA, n = 6), glutamine (GLN-EXA, n = 6) and DIP-EXA (n = 6), or to the exhaustion test followed by a recovery period lasting 3 hours: control (CON-REC, n = 6), glutamine (GLN-REC, n = 6) and DIP-REC (n = 6). The training protocol consisted of bouts of swimming exercise (60 min·day 1) for 6 weeks. During the last 21 days, before sacrifice, the glutamine and DIP groups received a daily dose of 1 g·kg 1 of glutamine and 1.5 g·kg 1 of DIP, respectively. The GLN-REC and DIP-REC groups were also supplemented immediately after the exhaustion test. Concentrations of glutamine, glutamate, glucose and ammonia in plasma and of glutamine, protein and glycogen in liver and muscle were evaluated. Results The time to exhaustion did not differ between groups. A higher concentration of glutamine in the gastrocnemius and soleus muscles was observed for the DIP-EXA group compared to the CON-EXA and GLN-EXA groups ( P < 0.05). The DIP-REC group presented a higher plasma and liver glutamine concentration than the CON-REC group ( P < 0.05). Muscle glutamine and protein concentration was higher in both the GLN-REC and DIP-REC groups compared to the CON-REC group ( P < 0.05). Conclusions Chronic supplementation with DIP promoted a higher muscle glutamine concentration than chronic supplementation with glutamine immediately after exercise. However, no significant difference in plasma or tissue glutamine concentrations was observed between acute supplementation with glutamine and DIP during the post-exhaustive exercise recovery period.

Metabolic pathways implicated in the kinetic impairment of muscle glutamine homeostasis in adult and old glucocorticoid-treated rats.

An impairment of muscle glutamine metabolism in response to dexamethasone (DEX) occurs with aging. To better characterize this alteration, we have investigated muscle glutamine release with regard to muscle glutamine production (net protein breakdown, de novo glutamine synthesis) in adult and old glucocorticoid-treated rats. Male Sprague-Dawley rats (3 or 24 mo old) were divided into seven groups: three groups received 1.5 mg/kg of DEX once a day by intraperitoneal injection for 3, 5, or 7 days; three groups were pair fed to the three treated groups, respectively; and one control group of healthy rats was fed ad libitum. Muscle glutamine synthetase activity increased earlier in old rats (day 3) than in adult rats (day 7), whereas an increase in muscle glutamine release occurred later in old rats (day 5) than in adult DEX-treated rats (day 3). Consequently, muscle glutamine concentration decreased later in old rats (day 5) than in adults (day 3). Finally, net muscle protein breakdown increased only in old DEX-treated rats (day 7). In conclusion, the impairment of muscle glutamine metabolism is due to a combination of an increase in glutamine production and a delayed increase in glutamine release.

Effects on skeletal muscle of intravenous glutamine supplementation to ICU patients

To evaluate the effect of four doses of intravenous glutamine supplementation on skeletal muscle metabolism. A prospective, blinded, randomized study. The general Intensive Care Unit (ICU) of a university hospital. ICU patients with multiple organ failure (n=40), who were expected to stay in the unit for more than five days. Patients received 0, 0.28, 0.57 or 0.86 g of glutamine per kg bodyweight per day intravenously for five days as part of an isocaloric, isonitrogenous and isovolumetric diet. Plasma glutamine concentration responded to glutamine supplementation with normalization of plasma levels in a dose-dependent way, while free muscle glutamine concentration, as well as muscle protein synthesis and muscle protein content, did not change significantly. Intravenous glutamine supplementation to ICU patients for a period of five days resulted in normalization of plasma glutamine concentrations in a dose-dependent way whereas muscle glutamine concentrations were unaffected.

Metabolic response of muscle to alanine, glutamine, and valine supplementation during severe illness.

Alanine and glutamine are released from muscle in response to critical illness. Subsequent depletion of glutamine from muscle is proposed as a principal factor in the limitation of muscle protein synthesis in severely ill patients. The objective of this study was to assess the peripheral metabolic response to enteral supplementation of alanine, glutamine, and valine in critically ill patients. Isotopic tracers of alanine, glutamine, and phenylalanine were given IV to 6 critically ill patients and 6 healthy volunteers. Blood sampling from the femoral artery and vein along with muscle biopsies provided assessment of leg (ie, muscle) kinetics. Measurements were obtained during enteral nutrition alone and then with combined alanine (11.25 g), glutamine (7.5 g) and valine (11.25 g) supplementation for 3 hours. Compared with healthy volunteers, critically ill patients had significantly reduced concentrations of alanine and glutamine in arterial plasma (p < .05), which increased significantly with amino acid supplementation. Muscle glutamine concentrations were significantly less in the patients and were not significantly affected by supplementation. Alanine and glutamine transport into and out of muscle and the rates of alanine and glutamine incorporation into and production from muscle were not affected by supplementation. Phenylalanine kinetics, as a marker of muscle protein metabolism, were not significantly altered by alanine, glutamine, and valine intake. These results demonstrate that alanine, glutamine, and valine administration fails to significantly affect muscle glutamine availability or muscle protein metabolism. These findings suggest that accelerated muscle catabolism in critically ill patients is not in response to any deficiency in alanine or glutamine availability.

Glutamine attenuates post-traumatic glutathione depletion in human muscle

Glutathione is quantitatively the most important endogenous scavenger system. Glutathione depletion in skeletal muscle is pronounced following major trauma and sepsis in intensive care unit patients. Also, following elective surgery, glutathione depletion occurs in parallel with a progressive decline in muscle glutamine concentration. The present study was designed to test the hypothesis that glutamine supplementation may counteract glutathione depletion in a human trauma model. A homogeneous group of patients (n = 17) undergoing a standardized surgical procedure were prospectively randomly allocated to receive glutamine (0.56g·day-1·kg-1) or placebo as part of isonitrogenous and isocaloric nutrition. Percutaneous muscle biopsies and blood samples were taken pre-operatively and at 24 and 72h after surgery. The concentrations of muscle glutathione and related amino acids were determined in muscle tissue and plasma. In the control (unsupplemented) subjects, total muscle glutathione had decreased by 47±8% and 37±11% and reduced glutathione had decreased by 53±10% and 45±16% respectively at 24 and 72h after surgery (P&lt;0.05). In contrast, in the glutamine-supplemented group, no significant post-operative decreases in total or reduced glutathione were seen following surgery. Muscle free glutamine had decreased at 72h after surgery in both groups, by 41.4±14.8% (P&lt;0.05) in the glutamine-supplemented group and by 46.0±14.3% (P&lt;0.05) in the control group. In conclusion, the present study demonstrates that intravenous glutamine supplementation attenuates glutathione depletion in skeletal muscle in humans following standardized surgical trauma.