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PubMed2001

Effect of glutamine supplementation on exercise-induced changes in lymphocyte function.

The purpose of this study was to investigate the possible role of glutamine in exercise-induced impairment of lymphocyte function. Ten male athletes participated in a randomized, placebo-controlled, double-blind crossover study. Each athlete performed bicycle exercise for 2 h at 75% of maximum O(2) consumption on 2 separate days. Glutamine or placebo supplements were given orally during and up to 2 h postexercise. The trial induced postexercise neutrocytosis that lasted at least 2 h. The total lymphocyte count increased by the end of exercise due to increase of both CD3(+)TCR alpha beta(+) and CD3(+)TCR gamma delta(+) T cells as well as CD3(-)CD16(+)CD56(+) natural killer (NK) cells. Concentrations of CD8(+) and CD4(+) T cells lacking CD28 and CD95 on their surface increased more than those of cells expressing these receptors. Within the CD4(+) cells, only CD45RA(-) memory cells, but not CD45RA(+) naive cells, increased in response to exercise. Most lymphocyte subpopulations decreased 2 h after exercise. Glutamine supplementation abolished the postexercise decline in plasma glutamine concentration but had no effect on lymphocyte trafficking, NK and lymphokine-activated killer cell activities, T cell proliferation, catecholamines, growth hormone, insulin, or glucose. Neutrocytosis was less pronounced in the glutamine-supplemented group, but it is unlikely that this finding is of any clinical significance. This study does not support the idea that glutamine plays a mechanistic role in exercise-induced immune changes.

Adult↗
PubMed1979

Effects of glutamine deprivation on glucose and amino acid metabolism in tissue culture.

The effects of glutamine deprivation on cultured skeletal muscle cells were analyzed by incubating 10-day-old myotube preparations in glutamine free Dulbecco's modified Eagle medium containing 10% fetal calf serum for up to 48 h. Under these conditions net glutamine production was not observed, but active ammonia production (average rate = 1.0 nmol/min . mg protein) continued despite glutamine withdrawal. Glutamine deprivation was associated with a progressive depletion of intracellular aspartate and glutamate. Maximal aspartate depletion correlated with a 15-fold increase in the intracellular lactate:pyruvate ratio and a 3-fold decrease in the estimated intracellular glutamate:(alpha-ketoglutarate) (ammonia) ratio. Despite wide shifts in cell metabolite concentrations, the mass action ratios of alanine and aspartate aminotransferase approximated the expected equilibria constants. These results suggest that 1) glutamine deprivation is associated with a marked reduction of aspartate, and the maintenance of aspartate depletion is due in part to the tendency of aspartate aminotransferase to maintain the metabolites of this reaction at a near equilibrium level; 2) the transport of reducing equivalents from the cytosolic to the mitochondrial compartments via the malate-aspartate shuttle may be limited under conditions of aspartate depletion.

Amino Acids↗
PubMed1980

Production of alanine and glutamine by atrial muscle from fed and fasted rats.

During incubation in vitro, rat atrial and rabbit papillary muscles synthesized and released large amounts of alanine and even higher amounts of glutamine. The amino groups used in the synthesis of alanine and glutamine appeared to be derived from the catabolism of other amino acids, specifically, leucine, isoleucine, valine, aspartate, glutamate, asparagine, arginine, and proline. The total amount of glutamine and alanine synthesized increased by 45% in atrial muscle from fasted rats, in which the oxidation of branched-chain amino acids is enhanced. In atria from fed rats, addition of leucine stimulated by about 20% the production of both alanine and glutamine, probably by providing additional amino groups for transamination with alpha-ketoglutarate. However, in cardiac muscle from fasted rats and rabbits, leucine increased the production of glutamine, but not of alanine. Isoleucine and valine, by contrast, enhanced production of both alanine and glutamine in these tissues. In the presence of leucine, low levels of pyruvate seem to limit the production of alanine, apparently because leucine, unlike isoleucine or valine, promotes the conversion of pyruvate to lactate.

Alanine↗
PubMed1986

Glutamine blocks lipolysis and ketogenesis of fasting.

Several in vivo studies have indirectly suggested a relationship between blood glutamine and ketonemia. The present study was designed to characterize the role glutamine plays in regulating lipolysis and ketogenesis during fasting in vivo. Twelve dogs had catheters implanted in the hepatic and portal veins (V) and in the femoral artery (A) 17-21 days before study. The animals were fasted for 4 days. After a 120-min rest and 40-min basal periods, 6 dogs received an infusion of L-glutamine at 6 mumol X kg-1 X min-1 and 6 received saline and acted as controls. Hepatic and splanchnic balances (mumol X kg-1 X min-1) were estimated by A-V differences multiplied by blood flow determined by indocyanine green. Fasting was associated with a compensated (no change in pH) mild metabolic acidosis but no change in plasma insulin and glucagon or blood glutamine. L-Glutamine infusion increased blood glutamine by 20% but decreased arterial free fatty acids (FFA, from 1,054 +/- 47 to 850 +/- 43 mumol/l, P less than 0.01), beta-hydroxybutyrate (beta-OHB, from 136 +/- 15 to 66 +/- 8 mumol/l, P less than 0.01), acetoacetate (AcAc, from 168 +/- 26 to 86 +/- 21 mumol/l, P less than 0.01), and glycerol (from 90 +/- 4 to 65 +/- 5 mumol/l, P less than 0.01). It also decreased hepatic uptake of glycerol (from 2.5 +/- 0.5 to 0.8 +/- 0.3 mumol X kg-1 X min-1, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1991

Role of leucine as a precursor of glutamine alpha-amino nitrogen in vivo in humans.

To assess the role of leucine as a precursor of glutamine alpha-amino N in vivo, five healthy men received primed continuous intravenous infusions of L-[15N]leucine, L-[15N]alanine, and L-[2-15N]glutamine in the postabsorptive state on three separate days and over 7, 4, and 4 h, respectively. A steady state in isotopic enrichment was observed in every amino acid during the last hour of each isotope infusion and was used to calculate the rates of amino acid appearance (Ra) and interconversion. Leucine, alanine, and glutamine Ra values were 137 +/- 18, 234 +/- 42, and 320 +/- 18 (SD) mumol.kg-1.h-1, respectively. Rates of N transfer from leucine to glutamine and alanine were 29 +/- 9 and 29 +/- 11 mumol.kg-1.h-1, respectively; these rates represented 21 +/- 8 and 21 +/- 12%, respectively, of leucine's N and 9 +/- 3 and 13 +/- 4% of glutamine's alpha-amino N and alanine N, respectively. These results suggest that the endogenous branched-chain amino acids released by protein breakdown are major precursors of both glutamine and alanine de novo synthesis in postabsorptive humans.

Adult↗
PubMed1994

Production of glutamine and utilization of glutamate by rat subcutaneous adipose tissue in vivo.

Information about adipose tissue amino acid metabolism is limited, with most data derived from studies in vitro. The purpose of this study was to further characterize the role of adipose tissue in glutamine metabolism in the rat in vivo. The extracellular concentrations of glutamine, glutamate, alanine, and ammonia were measured in the rat inguinal fat pad using a microdialysis sampling technique. A calibration method was used to accurately assess the extracellular levels of metabolites, and a comparison of these concentrations with those in arterial blood allowed determination of the net flux of each compound. The adipose tissue-arterial blood concentration differences were 122 +/- 19, 54 +/- 37, -61 +/- 21, and -28 +/- 13 microM for glutamine, alanine, glutamate, and ammonia, respectively, indicating a production of glutamine and an uptake of glutamate by subcutaneous adipose tissue. The magnitude of glutamine production suggests that adipose tissue may play a significant role in whole body glutamine homeostasis.

Adipose Tissue↗
PubMed2003

Enteral glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut mucosa.

Effects of glutamine on whole body and intestinal protein synthesis and on intestinal proteolysis were assessed in humans. Two groups of healthy volunteers received in a random order enteral glutamine (0.8 mmol.kg body wt(-1)x h(-1)) compared either to saline or isonitrogenous amino acids. Intravenous [2H5]phenylalanine and [13C]leucine were simultaneously infused. After gas chromatography-mass spectrometry analysis, whole body protein turnover was estimated from traced plasma amino acid fluxes and the fractional synthesis rate (FSR) of gut mucosal protein was calculated from protein and intracellular phenylalanine and leucine enrichments in duodenal biopsies. mRNA levels for ubiquitin, cathepsin D, and m-calpain were analyzed in biopsies by RT-PCR. Glutamine significantly increased mucosal protein FSR compared with saline. Glutamine and amino acids had similar effects on FSR. The mRNA level for ubiquitin was significantly decreased after glutamine infusion compared with saline and amino acids, whereas cathepsin D and m-calpain mRNA levels were not affected. Enteral glutamine stimulates mucosal protein synthesis and may attenuate ubiquitin-dependent proteolysis and thus improve protein balance in human gut.

Adult↗
PubMed2000

Effects of enteral glutamine on gut mucosal protein synthesis in healthy humans receiving glucocorticoids.

In hypercatabolic patients, the beneficial effects of glutamine on gut mucosa could be partly due to a stimulation of protein synthesis. The fractional synthesis rate (FSR) of gut mucosal protein was measured in four groups of healthy volunteers treated with glucocorticoids for 2 days. Two groups were studied in the postabsorptive state while receiving glutamine or a nitrogen equivalent (control) and two groups in the fed state with or without glutamine, using a 5-h intravenous infusion of [(13)C]leucine, [(2)H(5)]phenylalanine, and cortisone. After nutrient and tracer infusion, duodenal biopsies were taken. In the postabsorptive state, FSR of gut mucosal protein were 87 and 76%/day in the control group and 130% (P = 0.058 vs. control) and 104% (P = 0.17 vs. control)/day in the glutamine group, with leucine and phenylalanine as tracers, respectively. During feeding, FSR did not increase and no significant difference was observed between glutamine and control groups. Overall, FSR of the four groups were two- to threefold higher than those obtained previously in healthy humans, suggesting that glucocorticoids may increase gut mucosal protein synthesis. However, in this situation, a moderate enteral glutamine supply failed to demonstrate a significant effect on gut mucosal protein synthesis in the postabsorptive state and during feeding.

Administration, Oral↗
PubMed1993

Regulation of L-arginine synthesis from L-citrulline by L-glutamine in endothelial cells.

L-Arginine synthesis from L-citrulline was studied in cultured bovine venular, bovine aortic, human microvascular, and cloned human microvascular endothelial cells (EC). L-Citrulline was actively recycled into L-arginine in all four EC lines, with similar rates between venular and aortic EC. L-Arginine synthesis from L-citrulline was very sensitive to extracellular L-citrulline concentrations in the range normally found in plasma (50-100 microM). L-Glutamine (0.5mM) decreased L-arginine synthesis from L-citrulline, whereas 0.5 mM L-arginine, L-alanine, L-glutamate, or L-lysine had no effect. In contrast to the findings in intact cells, 1 mM L-glutamine had no effect on L-arginine synthesis from L-citrulline in EC lysates. Similarly, L-glutamine (1 mM) had no effect on the conversion of argininosuccinate to arginine in EC lysates. L-Glutamine (0.5 and 1 mM), but not 0.5 mM L-arginine, L-alanine, L-glutamate, or L-lysine, inhibited L-citrulline transport by EC. The inhibition of L-citrulline transport by L-glutamine was dose dependent and competitive in nature. These results suggest that L-glutamine decreased L-arginine synthesis from extracellular L-citrulline by interfering with its transport. Inasmuch as nitric oxide (NO) and L-citrulline are constantly generated from L-arginine, with L-citrulline being actively converted into L-arginine in venular, microvascular, and aortic EC, our data indicate a functioning intracellular arginine-citrulline cycle in these cells. This cycle may function to efficiently scavenge the carbon and alpha-amino group of L-arginine and to maintain a sufficient cellular concentration of L-arginine during prolonged synthesis of NO in EC. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

Glutamine transport by mitochondria isolated from normal and acidotic rats.

The transport of L-glutamine by isolated rat renal mitochondria was studied by means of a rapid-filtration (Millipore Filter Corp.) technique. The movement of glutamine from the incubation medium into the inner mitochondrial compartment (matrix) was inhibited by structural analogues (6-diazo-5-oxo-L-norleucine and glutamic acid), sulghydryl-binding agents (p-chloromercuri-benzoate and mersalyl), and inhibitors of mitochondrial oxidative metabolism (azide, antimycin A, and uncouplers of oxidative phosphorylation). These results suggest that glutamine is transported across the inner membrane of renal mitochondria by a carrier-mediated system that is linked to the processes of oxidative metabolism. The transport of glutamine by isolated renal mitochondria was increased two- to threefold by chronic (5-7 days) metabolic acidosis. However, short-term metabolic acidosis did not increase the glutamine transport capacity of isolated mitochondria. A hypothesis is presented for the regulation of mitochondrial glutamine transport, in vivo, during short-term and chronic acidosis.

Acidosis↗
PubMed1984

Glutamine transport in renal basolateral vesicles from dogs with metabolic acidosis.

To determine whether the increased ammonia production per nephron in chronic metabolic acidosis is accompanied by augmented L-glutamine transport across the basolateral membrane of the renal cortical cell and consequent increased availability of this ammoniagenic amino acid, we measured L-[3H]glutamine transport in basolateral membrane vesicles (BLMV) isolated from kidneys of normal and acidotic dogs. Na+ -dependent electrogenic transport of L-[3H]glutamine was demonstrated in BLMV from kidneys of normal dogs that exhibited saturability over the concentration range of 25 microM to 2 mM L-glutamine. The apparent Km was 416 +/- 114 microM and Vmax was 536 +/- 129 pmol X mg protein-1 X 15 s-1. The initial rate of Na+ -dependent L-[3H]glutamine transport was increased in BLMV from kidneys of acidotic dogs, as reflected by an increased apparent Vmax. We conclude that an adaptation resulting in greater uptake of L-glutamine across the basolateral membrane of the renal cortical cell may underlie, in part, the increased rate of ammonia production per nephron seen in chronic metabolic acidosis.

Acidosis↗
PubMed1984

Glutamine transport in basolateral vesicles from dogs with acute respiratory acidosis.

It has been shown that acute respiratory acidosis in dogs results in enhanced renal extraction of L-glutamine from plasma and increased ammonia excretion per nephron. To determine whether a component of the enhanced L-glutamine extraction results from increased transport of L-glutamine across the basolateral membrane into the renal proximal tubular cell, we measured Na+ gradient-dependent L-[3H]glutamine transport in proximal tubular basolateral membrane vesicles isolated from kidneys of normal dogs and from kidneys of dogs following 2 h of acute respiratory acidosis. The initial rate of Na+ gradient-dependent L-[3H] glutamine uptake (15 s) was increased significantly in basolateral membrane vesicles from the acidotic compared with normal dogs. Increased uptake could be measured under conditions in which changes in membrane potential resulting from fluxes of solute were minimized. We conclude that an adaptation occurs in the basolateral membrane of the renal proximal tubular cell during acute respiratory acidosis that allows increased transport of L-glutamine across the membrane into the proximal tubular cell. This adaptation may permit increased ammonia production per nephron.

Acid-Base Equilibrium↗
PubMed2001

Glutamine induces heat shock protein and protects against endotoxin shock in the rat.

Enhanced expression of heat shock protein (HSP) has been shown to be protective against laboratory models of septic shock. Induction of HSPs to improve outcome in human disease has not been exploited because laboratory induction agents are themselves toxic and not clinically relevant. In this study, we demonstrate that a single dose of intravenous glutamine causes a rapid and significant increase in HSP25 and HSP72 expression in multiple organs of the unstressed Sprague-Dawley rat. With the utilization of a fluid-resuscitated rat model of endotoxemia, mortality was dramatically reduced by glutamine administration concomitant with the endotoxin injury. Endotoxin-treated animals given glutamine exhibited dramatic increases in tissue HSP expression and marked reduction of end-organ damage. These data suggest glutamine may protect against mortality and attenuate end-organ injury in endotoxemic shock via enhanced HSP expression. Furthermore, glutamine confers protection when administered at the initiation of sepsis, rather than as pretreatment. Thus glutamine appears to be a clinically viable enhancer of HSP expression and may prove beneficial in the therapy of sepsis and sepsis-induced organ injury.

Ammonia↗
PubMed1993

Utilization of glutamine and of TCA cycle constituents as precursors for transmitter glutamate and GABA.

In the present review evidence is presented that (1) glutamine synthesis in astrocytes is essential for synthesis of GABA in neurons; (2) alpha-ketoglutarate in the presence of alanine (as an amino group donor) can replace glutamine as a precursor for synthesis of transmitter glutamate, but maybe not as a precursor for transmitter GABA; (3) differences exist in the intraneuronal metabolic pathways for utilization of alpha-ketoglutarate plus alanine and of glutamine, and (4) alanine also functions as a substrate for oxidative metabolism in glutamatergic neurons. It should be emphasized that the supply of precursors for transmitter glutamate and GABA in glutamatergic and GABAergic neurons depends on metabolic processes in astrocytes regardless whether glutamine or alpha-ketoglutarate plus L-alanine function as the transmitter precursors. The key reason that an interaction with astrocytes is essential is that both pyruvate carboxylase, the major enzyme in the brain for net synthesis of tricarboxylic acid cycle intermediates, and glutamine synthetase, the enzyme forming glutamine from glutamate, are specifically located in astrocytes, but not in neurons.

Animals↗
PubMed1981

Correlation between glutamate deamination and glutamine deamidation in rat kidney mitochondria.

Intramitochondrial glutamate removal through deamination may regulate renal ammoniagenesis from glutamine. However, little information is available to determine if there is a strong association between glutamine deamidation and the removal within mitochondria of the glutamate subsequently formed after deamidation. Using rat renal mitochondria, we found that ammonia production, glutamate appearance, and amide nitrogen disappearance were near equal aerobically and anerobically, when no ADP-generating system was present. When an ADP-generating system was added (ATP alone, ATP+ malonate, or ATP+2,4 DNP), more ammonia was formed aerobically from glutamine. Additionally, less glutamate appeared even though more amide nitrogen disappeared. Intramitochondrial concentrations of glutamate decreased. When pyruvate and alpha-ketoglutarate were added to the system, ammoniagenesis, deamidation, and deamination decreased; while glutamate built up in both the medium and mitochondria. In our mitochondrial system, we found a significantly positive correlation between glutamate deamination and glutamine deamidation, between glutamate accumulation and intramitochondrial glutamate concentrations; and a significantly negative correlation between glutamate deamination and glutamate accumulation, between glutamine deamidation and intramitochondrial glutamate concentrations, and between glutamate deamination and glutamate accumulation. We conclude that there is a biochemical relationship between glutamine deamidation and deamination of the glutamate subsequently formed. We propose that increased deamination lowers mitochondrial concentrations of glutamate and increases deamidation. In contrast, slowing deamination increases mitochondrial concentrations of glutamate and decreases deamidation.

Adenosine Diphosphate↗
PubMed1992

Restoration of cerebrovascular CO2 responsivity by glutamine synthesis inhibition in hyperammonemic rats.

Hyperammonemia increases brain glutamine levels, causes astrocytic swelling, and depresses cerebral blood flow (CBF) responsivity to CO2. Methionine sulfoximine (MSO) inhibition of glutamine synthetase activity, known to be enriched in astrocytes, prevents ammonia-induced increases in brain glutamine and water content. We tested the hypothesis that inhibition of glutamine accumulation restores CBF responsivity to CO2 during acute hyperammonemia. Pentobarbital-anesthetized rats treated with either vehicle or MSO (150 mg/kg i.p.) received a 6-hour intravenous infusion of either sodium or ammonium acetate. With subsequent induction of hypercapnia, CBF increased from 113 +/- 14 (mean +/- SEM) to 194 +/- 9 ml/min per 100 g in control rats but was unchanged from 107 +/- 13 to 79 +/- 10 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats restored the CBF response to hypercapnia (from 73 +/- 8 to 141 +/- 14 ml/min per 100 g). With induction of hypocapnia, CBF decreased from 114 +/- 11 to 88 +/- 11 ml/min per 100 g in control rats but increased from 112 +/- 13 to 142 +/- 19 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats did not fully restore the response to hypocapnia but prevented the paradoxical increase in CBF (from 80 +/- 8 to 80 +/- 8 ml/min per 100 g). In control rats, MSO did not affect CO2 responsivity. Treatment with MSO prevented ammonia-induced increases in intracranial pressure. Hyposmotic-induced increases in brain water content and intracranial pressure attenuated the CBF response to hypercapnia but, unlike hyperammonemia, did not attenuate the response to hypocapnia. In contrast to hypercapnia, vasodilation in response to arterial hypotension was intact in hyperammonemic rats. We conclude that the grossly abnormal CBF responsivity to CO2 alterations during hyperammonemia is linked to glutamine accumulation rather than ammonia per se. Cerebral edema secondary to glutamine accumulation may contribute in part to abnormal CBF responses, although other aspects of astrocyte dysfunction are likely to be important.

Ammonia↗
PubMed1996

Impaired pial arteriolar reactivity to hypercapnia during hyperammonemia depends on glutamine synthesis.

BACKGROUND AND PURPOSE: Acute hyperammonemia causes glutamine and water accumulation in astrocytes and loss of the cerebral blood flow response selectively to CO2. We tested whether extraparenchymal pial arterioles not subjected directly to mechanical compression by swollen astrocyte processes also lose hypercapnic reactivity and whether any such loss can be attenuated by inhibiting glutamine synthesis during hyperammonemia. METHODS: Pentobarbital-anesthetized rats were pretreated intravenously with either saline vehicle, methionine sulfoximine (0.83 mmol/kg), which inhibits glutamine synthetase and potentially gamma-glutamylcysteine synthetase, or buthionine sulfoximine (4 mmol/kg), which inhibits gamma-glutamylcysteine synthetase. Three hours after pretreatment, cohorts received an intravenous infusion of either sodium or ammonium acetate for 6 hours. Pial arteriolar diameter was measured with radiolabeled microspheres during normocapnia and 10 minutes of hypercapnia. RESULTS: With sodium acetate infusion, pial arteriolar diameter increased during hypercapnia in groups pretreated with vehicle (23+/-3% [mean+/-SE]; n=6), methionine sulfoximine (37+/-11%; n=5), and buthionine sulfoximine (32+/-3%; n=5). With ammonium acetate infusion, pial arteriolar diameter increased only in the group pretreated with methionine sulfoximine (31+/-4%; n=8) but not in those pretreated with vehicle (-2+/-4%; n=8) or buthionine sulfoximine (4+/-4%; n=6). Methionine sulfoximine, but not buthionine sulfoximine, also prevented loss of the cerebral blood flow response to hypercapnia, an increase in cortical tissue water content, and an increase in pressure under the cranial window during normocapnia in hyperammonemic rats. In contrast to hypercapnia, hypoxemia increased arteriolar diameter 30+/-7% (n=5) during ammonium acetate infusion. CONCLUSIONS: Loss of the blood flow response to hypercapnia during acute hyperammonemia is not due simply to swollen astrocyte processes passively impeding blood flow because extraparenchymal resistance arterioles also lose their reactivity selectively to hypercapnia. Lost reactivity depends on glutamine synthesis rather than on ammonium ions per se and may reflect indirect effects of astrocyte dysfunction associated with glutamine accumulation or possibly effects of glutamine on nitric oxide production.

Acetates↗
PubMed1978

Skeletal muscle protein and amino acid metabolism in experimental chronic uremia in the rat: accelerated alanine and glutamine formation and release.

The kinetics and factors regulating alanine and glutamine formation and release were investigated in skeletal muscle preparations from control and experimentally uremic rats. These preparations maintained phosphocreatine and ATP levels in vitro which closely approximated levels found in vivo. Alanine and glutamine release from uremic muscle were increased 45.8 and 36.0%, respectively, but tissue levels were unaltered. The increased release of alanine by uremic muscle was not accounted for by decreased rates of medium alanine reutilization via oxidation to CO(2) or incorporation into muscle protein. The maximal capacity of added amino acids such as aspartate, cysteine, leucine, and valine to stimulate net alanine and glutamine formation was the same in uremic and control muscle. Epitrochlearis preparations were partially labeled in vivo with [guanido-(14)C]-arginine. On incubation, preparations from uremic animals showed a 54.6% increase in the rate of loss of (14)C-label in acid precipitable protein. Correspondingly, these same uremic preparations showed a 62.7% increase in (14)C-label appearance in the acid-soluble fraction of muscle and in the incubation media. Insulin decreased alanine and glutamine release to an extent threefold greater in uremic than in control preparations, and increased muscle glucose uptake approximately threefold in all preparations. Although basal rates of [4,5-(3)H]leucine incorporation into protein were decreased 25% in uremic muscles as compared with control muscles, insulin stimulated [(3)H]leucine incorporation nearly equally in both preparations. These data demonstrate increased alanine and glutamine production and release from skeletal muscle of chronically uremic rats. This increase appears to derive in part from an enhancement of net protein degradation which could be caused by an acceleration in the breakdown of one or more groups of muscle proteins, or by an inhibition of protein synthesis, or by both processes. The increased alanine and glutamine formation and release in uremia appears not to result from an insensitivity to insulin action. The implications of these findings for an understanding of the abnormal carbohydrate metabolism of uremia are discussed.

Adenosine Diphosphate↗