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Biomedical subjects

D Darmaun

Publications and source records attributed to D Darmaun.

At least 37 records · Page 2Linked to original sources
PubMed1999

Leucine metabolism in preterm infants receiving parenteral nutrition with medium-chain compared with long-chain triacylglycerol emulsions.

BACKGROUND: Although medium-chain triacylglycerols (MCTs) may be utilized more efficiently than long-chain triacylglycerols (LCTs), their effect on protein metabolism remains controversial. OBJECTIVE: The aim of the study was to compare the effects of mixed MCT-LCT and pure LCT emulsions on leucine metabolism in preterm infants. DESIGN: Fourteen preterm [gestational age: 30+/-1 wk; birth weight: 1409+/-78 g (x +/- SE)] neonates were randomly assigned to receive, from the first day of life, either a 50:50 MCT-LCT (mixed MCT group; n = 7) or an LCT (LCT group; n = 7) lipid emulsion as part of an isonitrogenous, isoenergetic total parenteral nutrition program. On the fourth day, infants received intravenous feeding providing 3 g lipid, 15 g glucose, and 3 g amino acids kg(-1) x d(-1) and underwent 1) indirect calorimetry and 2) a primed, 2-h infusion of H13CO3Na to assess the recovery of 13C in breath, immediately followed by 3) a 3-h infusion of L-[1-13C]leucine. RESULTS: The respiratory quotient tended to be slightly but not significantly higher in the mixed MCT than in the LCT group (0.96+/-0.06 compared with 0.93+/-0.03). We did not detect a significant difference between the mixed MCT and LCT groups with regard to release of leucine from protein breakdown (B; 309+/-40 compared with 257+/-46 micromol x kg(-1) x h(-1)) and nonoxidative leucine disposal (NOLD; 296+/-36 compared with 285+/-49 micromol x kg(-1) x h(-1)). In contrast, leucine oxidation was greater in the mixed MCT than in the LCT group (113+/-10 compared with 67+/-10 micromol x kg(-1) x h(-1); P = 0.007). Net leucine balance (NOLD - B) was less positive in the mixed MCT than in the LCT group (-14+/-9 compared with 28+/-10 micromol x kg(-1) x h(-1); P = 0.011). CONCLUSION: Mixed MCTs may not be as effective as LCT-containing emulsions in promoting protein accretion in parenterally fed preterm neonates.

Bicarbonates↗
PubMed1999

Determination of glutamine in muscle protein facilitates accurate assessment of proteolysis and de novo synthesis-derived endogenous glutamine production.

BACKGROUND: Results of tracer studies indicate that skeletal muscle contributes to approximately 70% of overall glutamine production in healthy adults; the contribution of de novo synthesis being estimated at approximately 60%. However, measurement of the de novo synthesis rate in muscle tissue requires knowledge of the appearance rate of glutamine in plasma and the quantity of glutamine derived from intracellular proteolysis. Thus, the content of glutamine in muscle protein is a prerequisite for an accurate calculation. OBJECTIVE: The objective of the study was to measure glutamine in muscle protein. DESIGN: Muscle specimens (open biopsies) were obtained from humans (10 men and 4 women), rats (n = 4), cows (n = 4), and pigs (n = 4). Glutamine was assessed via prehydrolysis derivatization, rapid microwave-enhanced acid hydrolysis, and 5-dimethylaminonaphthalene-1-sulfonyl chloride (dansyl chloride) reversed-phase HPLC, and expressed per mg alkali-soluble protein (ASP) and DNA. RESULTS: Glutamine concentrations in muscle cell protein of various species ranged from 41 to 49 microg/mg ASP; the differences were not species related. The combined means (+/-SDs) for the 4 species were 43.6 +/- 4.9 microg/mg ASP and 11.9 +/- 2.0 mg/mg DNA, respectively. In humans, there was no apparent influence of age, sex, or BMI. CONCLUSIONS: Direct and specific measurements of glutamine in intact muscle protein were 50% lower than assumed previously. We used data compiled from earlier studies to recalculate the contributions of proteolysis and de novo synthesis to the endogenous production of glutamine in selected age groups of healthy humans; these contributions remained remarkably constant at approximately 13% and approximately 87%, respectively.

Adolescent↗
PubMed1999

Role of nutrients in the regulation of in vivo protein metabolism in humans.

Nutrients regulate protein metabolism both in an acute fashion and on a long-term basis. The ingestion of meals is associated with a dramatic switch from an overall catabolic state to a state of net protein anabolism. The acute response of protein metabolism to meal ingestion is mediated, in part, by an increase in insulin secretion, itself a consequence of glucose absorption. Whereas insulin may primarily suppress rates of proteolysis, amino acids are responsible for the stimulation of protein synthesis that follows food intake. In the long run, the effects of nutrition on protein metabolism depend on the energy supply, the source of the energy (carbohydrate versus fat) and dietary protein intake. Finally, specific amino acids, such as glutamine, may play an additional role as protein anabolic agents.

Amino Acids↗
PubMed1999

Effect of intravenous glutamine on duodenal mucosa protein synthesis in healthy growing dogs.

To determine whether glutamine acutely stimulates protein synthesis in the duodenal mucosa, five healthy growing dogs underwent endoscopic biopsies of duodenal mucosa at the end of three 4-h primed, continuous intravenous infusions of L-[1-13C]leucine on three separate days, while receiving intravenous infusion of 1) saline, 2) L-glutamine (800 micromol. kg-1. h-1), and 3) isonitrogenous amounts of glycine. The three infusions were performed after 24 h of fasting, a week apart from each other and in a randomized order. Glutamine infusion induced a doubling in plasma glutamine level, and glycine caused a >10-fold rise in plasma glycine level. During intravenous infusions of [13C]leucine, the plasma leucine labeling attained a plateau value between 3.22 and 3.68 mole % excess (MPE) and [13C]ketoisocaproate ([13C]KIC) of 2.91-2. 84 MPE; there were no significant differences between glutamine, glycine, and saline infusion days. Plasma leucine appearance rate was 354 +/- 33 (SE), 414 +/- 28, and 351 +/- 35 micromol. kg-1. h-1 (not significant) during glycine, saline, and glutamine infusion, respectively. The fractional synthetic rate (FSR) of duodenal mucosa protein was calculated from the rise in protein-bound [13C]leucine enrichment in the biopsy sample, divided by time and with either plasma [13C]KIC or tissue free [13C]leucine as precursor pool enrichment. Regardless of the precursor pool used in calculations, duodenal protein FSR failed to rise significantly during glutamine infusion (65 +/- 11%/day) compared either with saline (84 +/- 18%/day) or glycine infusion days (80 +/- 15%/day). We conclude that 1) plasma [13C]KIC and tissue free [13C]leucine can be used interchangeably as precursor pools to calculate gut protein FSR; and 2) short intravenous infusion of glutamine does not acutely stimulate duodenal protein synthesis in well-nourished, growing dogs.

Aging↗
PubMed1998

Whole-body protein metabolism assessed by leucine and glutamine kinetics in adult patients with active celiac disease.

To assess the effect of increased renewal of intestinal epithelial cells on leucine and glutamine (Gln) turnover, 4-hour intravenous infusions of L-[1-(13)C]leucine and L-[2-(15)N]Gln were administered to five adult patients with active celiac disease in the postabsorptive state. There was a 35% increase in leucine flux (micromoles per kilogram per hour) in patients (117 +/- 17) compared with healthy controls (96 +/- 11, P < .03). Gln flux was increased by 13% in patients (377 +/- 35) versus controls (335 +/- 16, P < .04). These results suggest that active celiac disease, characterized by villous atrophy and crypt cell hyperplasia, is associated with a dramatic increase in whole-body protein breakdown as assessed by 13C-leucine, which may contribute per se to the protein malnutrition status of the patients. The increase in Gln utilization as assessed by L-[2-(15)N]Gln was moderate, but may have been offset due to the villose atrophy and ensuing reduced intestinal epithelial cell mass. The results are consistent with the concept that increased renewal of intestinal epithelial cells represents a sizable fraction of whole-body protein turnover and that Gln is an important fuel for epithelial intestinal cells in vivo.

Adult↗
PubMed1998

Hyperglucagonemia and the immediate fate of dietary leucine: a kinetic study in humans.

The possible role of glucagon in determining the fate of dietary absorbed amino acids within the splanchnic bed was investigated in five healthy male volunteers. A kinetic study was performed involving a continuous 240-minute infusion of L-[5,5,5-2H3]leucine and D-[6,6-2H2]glucose by vein, while L-[1-13C]leucine was infused by a feeding tube into the duodenum (intragut [i.g.]) along with a constant intravenous (i.v.) infusion of somatotropin release-inhibitory factor (SRIF) combined with insulin, growth hormone, and glucagon. In random order, glucagon was infused at a rate of 0.4 ng x kg(-1) x min(-1) in one experiment and 1.2 ng x kg(-1) x min(-1) in the other experiment, while insulin and growth hormone were kept at constant serum levels, respectively, 37+/-13 pmol x L(-1) and 5+/-0.2 microg x L(-1). The diet was provided as an L-amino acid solution including 60 micromol x kg(-1) x h(-1) leucine without fat and carbohydrate. During the higher rate of glucagon infusion, there was an increase in plasma glucagon and glucose concentrations, glucose flux, and net dietary leucine release into the periphery from the splanchnic bed. Splanchnic removal and uptake of leucine were decreased with increased glucagon infusion. There were no statistical differences in the plasma leucine level and i.v. and i.g. leucine fluxes at the two glucagon levels, although leucine metabolic clearance increased (0.74 v 0.85 L x kg(-1) x h(-1), P=.08) in the case of glucagon excess. Plasma glucose increased with glucagon excess and was negatively correlated (P < .05) with the plasma leucine level (r=-.348) and i.v. (r=-.459) or i.g. (r=-.359) leucine fluxes. The negative correlation between plasma glucagon and leucine levels was also significant (r=-.684). No significant correlation was found between dietary leucine splanchnic removal and glucose, glucagon, or leucine plasma concentrations. We conclude that glucagon in excess has only a small quantitative effect on the overall handling of dietary leucine, and hypothesize that more leucine is exported to the peripheral tissues under these hormonal conditions.

Adult↗
PubMed1998

Role of glucose and glutamine synthesis in the differential recovery of 13CO2 from infused [2-13C] versus [1-13C] acetate.

Carbon exchange in the Krebs cycle may result in underestimation of substrate oxidation measured with 13C-labeled substrates, since carbon labeled in position 2 of acetyl-coenzyme A (CoA) could be incorporated into glucose (via gluconeogenesis) and glutamine. Five healthy volunteers were therefore infused with [1-13C] and [2-13C] acetate at a rate of 0.5 micromol x kg(-1) x min(-1) for 165 minutes on two different occasions in randomized order. Whole body acetate turnover did not differ between the two tracers: 7.9+/-0.3 and 7.5+/-0.6 micromol x kg(-1) x min(-1) (nonsignificant [NS]) for [1-13C] and [2-13C] acetate, respectively. Isotopic 13C enrichment was higher in expired CO2 (0.177+/-0.021 v 0.089+/-0.009 atom percent excess [APE], P < .01) and lower in glucose (0.074+/-0.017 v0.291+/-0.061 mole percent excess [MPE], P < .01) for [1-13C] acetate compared with [2-13C] acetate, respectively, at the end of the infusions. Glutamine isotopic enrichment was slightly but not significantly higher when infusing [1-13C] acetate versus [2-13C] acetate (0.348+/-0.038 v0.495+/-0.069 MPE, NS, respectively). At the end of the experiment, the recovery of 13CO2 from [1-13C] acetate was 44.8%+/-2.7%, and from [2-13C] acetate, 22.6%+/-1.3%. A significant correlation was observed between the differences in 13C enrichment of CO2 for the two tracers and glucose (deltaCO2=0.424 x deltaglucose + 0.001, R2=.9856, P=.0007) or glutamine (deltaCO2=0.621 x deltaglutamine + 0.004, R2=.9573, P=.0038) during the infusion. These results suggest that (1) although gluconeogenesis appears to be more responsible than glutamine for the differential recovery of [2-13C] versus [1-13C] acetate, other secondary pathways are probably also implicated; and (2) different recovery correction factors should be applied when measuring substrate oxidation with a stable isotope tracer depending on the expected position of 13C in acetyl-CoA.

Acetates↗
PubMed1998

Production rate of acetate during colonic fermentation of lactulose: a stable-isotope study in humans.

BACKGROUND: Breath tests are currently used to qualitatively assess colonic fermentation; no quantitative estimations are available for healthy subjects. OBJECTIVE: This study describes a stable-isotope-dilution method to measure acetate production quantitatively from colonic bacterial fermentation. DESIGN: Six volunteers received a primed, constant, intravenous infusion of [1-13C]acetate at a rate of 1.01 +/- 0.04 micromol x kg(-1) x min(-1) for 7 h. They ingested 20 g pure lactulose after 1 h of the tracer infusion. Expired air and arterialized venous blood were sampled every 15 min. RESULTS: Before lactulose intake, the breath-hydrogen concentration was 7 +/- 2 ppm and the plasma acetate concentration and isotopic enrichment were 141 +/- 14 micromol/L and 14.8 +/- 1.4 moles percent excess, respectively. Whole-body acetate turnover was 6.0 +/- 0.7 micromol x kg(-1) x min(-1). After lactulose ingestion, maximum breath hydrogen and acetate concentrations reached 63 +/- 15 ppm (P = 0.004) and 313 +/- 25 micromol/L (P = 0.002), respectively, whereas [13C]acetate enrichment decreased to 9.9 +/- 1.3 moles percent excess (P = 0.03). Whole-body acetate turnover increased to 9.8 +/- 1.5 micromol x kg(-1) x min(-1) and later decreased almost to baseline values. Colonic lactulose fermentation yielded 140 +/- 12 mmol acetate over 6 h, representing 86% of the production based on stoichiometric equations. CONCLUSION: This new method provides a quantitative estimate of colonic carbohydrate fermentation via evaluation of acetate production.

Acetates↗
PubMed1998

Whole-body, peripheral and intestinal endogenous acetate turnover in dogs using stable isotopes.

Acetate metabolism supplies about 10% of energy requirements in food-deprived nonruminant animals. This study used a stable isotope dilution method to investigate the fate of acetate in 24-h food-deprived dogs free of colonic fermentation. Three dogs received intravenous bolus injections of 40 or 70 micromol/kg of [1-13C] acetate, and carotid blood was then sampled during a 15-min period to estimate the acetate distribution volume. Ten dogs received intravenous [1-13C] acetate infusions of 1.05 +/- 0.02 or 2.10 +/- 0. 10 micromol/(kg.min) for 120 or 200 min after a prime of 200 or 70 micromol/kg, respectively. Cephalic venous and carotid arterial blood were sampled for all dogs, and portal blood for five. Acetate distribution volume was 0.27 +/- 0.16 L/kg (mean +/- SEM). The concentrations of acetate in arterial (144 +/- 17 micromol/L), venous (155 +/- 20 micromol/L) and portal plasma (131 +/- 16 micromol/L) were not significantly different during infusion, whereas isotopic enrichments [mole percent excess (MPE): labeled acetate/all acetate molecules] in portal (1.2 +/- 0.2 MPE) and venous plasma (1.7 +/- 0.3 and 2.6 +/- 0.7 MPE) were lower than in arterial plasma for both infusion rates (4.9 +/- 0.6 and 7.6 +/- 0.8 MPE, respectively, P < 0.005). Whole-body acetate turnover was 24.4 +/- 2.4 micromol/(kg.min). Fractional acetate extractions for forelimb and intestine were 62 +/- 7 and 72 +/- 6%, respectively, and the production for each organ was 0.3 and 1.1 micromol/(kg.min) respectively, similar to that of utilization (P > 0.05). It is concluded that the forelimb and intestine produce and utilize acetate as an energy source in 24-h food-deprived dogs free of colonic fermentation.

Acetates↗
PubMed1998

Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism.

The present study was designed to determine whether sodium phenylbutyrate (phi B) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g.kg-1.day-1) of phi B were administered for 24 h before study: postabsorptive plasma glutamine concentration declined in a dose-dependent manner, achieving an approximately 25% decline for a dose of 0.36 g phi B.kg-1.day-1. A second group of six healthy adults received 5-h infusions of L-[1-14C]leucine and L-[1-13C]glutamine in the postabsorptive state on two separate days: 1) under baseline conditions and 2) after 24 h of oral treatment with phi B (0.36 g.kg-1.day-1) in a randomized order. The 24-h phenylbutyrate treatment was associated with 1) an approximately 26% decline in plasma glutamine concentration from 514 +/- 24 to 380 +/- 15 microM (means +/- SE; P < 0.01 with paired t-test) with no change in glutamine appearance rate or de novo synthesis; 2) no change in leucine appearance rate (Ra), an index of protein breakdown (123 +/- 7 vs. 117 +/- 5 mumol.kg-1.h-1; not significant); 3) an approximately 22% rise in leucine oxidation (Ox) from 23 +/- 2 to 28 +/- 2 mumol.kg-1.h-1 (P < 0.01), resulting in an approximately 11% decline in nonoxidative leucine disposal (NOLD = Ra-Ox), an index of protein synthesis, from 100 +/- 6 to 89 +/- 5 mumol.kg-1.h-1 (P < 0.05). The data suggest that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a "glutamine trap" to create a model of glutamine depletion; 2) a moderate decline in plasma glutamine does not enhance rates of endogenous glutamine production; and 3) a short-term depletion of plasma glutamine decrease estimates of whole body protein synthesis.

Adult↗
PubMed1998

Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy.

We determined whether glutamine has a protein anabolic effect in six 8-13-y-old boys with Duchenne muscular dystrophy. Children received a 5-h i.v. infusion of L-[1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state on two consecutive days while drinking: 1) flavored water on one day, and 2) the same drink mixed with L-glutamine (800 micromol x kg[-1] x h[-1]), the other day. Oral glutamine administration was associated with an 8% decrease in leucine release from protein breakdown, from 116 +/- 5 to 107 +/- 6 micromol x kg(-1) h(-1) (p < 0.01), and a 35% decrease in leucine oxidation rate from 23 +/- 2 to 15 +/- 2 micromol x kg(-1) x h(-1) (p < 0.01), resulting in no change in the nonoxidative leucine disposal, an index of protein synthesis. Whole body glutamine exchange in plasma doubled from 321 +/- 22 to 623 +/- 24 micromol x kg(-1) x h(-1), p < 0.01, but glutamine from protein degradation and glutamine de novo synthesis both decreased (91 +/- 4 versus 84 +/- 5 micromol x kg(-1) x h(-1), p < 0.01, and 230 +/- 21 versus 163 +/- 25 micromol x kg(-1) x (h-1), p = 0.02, respectively). These data suggest that acute oral glutamine administration might have a protein-sparing effect in children with Duchenne muscular dystrophy, decreasing estimates of whole body protein degradation and glutamine de novo synthesis, therefore sparing nitrogen precursors.

Administration, Oral↗
PubMed1997

Determination of low 13C-glutamine enrichments using gas chromatography-combustion-isotope ratio mass spectrometry.

Glutamine is an essential fuel for tissues with high rates of cell replication, such as enterocytes and lymphocytes. Infusion of 13C-labeled glutamine tracers allows for measurement of the rates of production, utilization and oxidation of glutamine's carbon skeleton in vivo. The use of this tracer, however, has been limited by its high cost and/or the difficulty is measuring low enrichments in biological fluids using conventional gas chromatography-mass spectrometry (GC/MS) techniques. We have developed a method using gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) that allows for the determination of low 13C enrichments (down to 0.06 mol.% excess) with a precision of 2% or better, and a within-day and between-day variability better than 5%, in plasma free glutamine. The method was applied to measuring the incorporation of 13C in plasma glutamine over the course of infusion of 13C-labeled acetate in a human subject.

Carbon Isotopes↗
PubMed1997

Energy and protein metabolism during recovery from malnutrition due to nonneoplastic gastrointestinal disease.

The magnitude of metabolic adaptation to malnutrition is still debated and few studies have investigated the phase of recovery from malnutrition. The aim of the present work was to determine whether refeeding was associated with adaptive changes in 1) energy expenditure, 2) maximal capacity for oxidizing lipids, and 3) whole-body protein turnover. Eleven malnourished patients with nonneoplastic gastrointestinal diseases were studied by using indirect calorimetry and L-[1-13C]leucine infusion while being infused with lipid-rich total parenteral nutrition (TPN). The same study was performed before initiation of TPN and after a mean gain of 6.5 kg body wt. In absolute values, resting energy expenditure (REE) increased after refeeding (4.05 +/- 0.85 compared with 4.60 +/- 1.05 MJ/d). Change in REE adjusted for fat-free mass (FFM) correlated significantly with change in body weight (r = 0.850, P = 0.01) and change in body fat (r = 0.798, P = 0.01) but not with change in FFM (r = -0.06, NS). Lipid oxidation decreased significantly after body weight gain (0.93 +/- 0.28 compared with 0.50 +/- 0.37 mg.kg-1.min-1). When expressed per kg FFM, protein turnover and breakdown increased significantly during body weight gain. Moreover, the change in protein turnover correlated with the rate of change in FFM, suggesting that FFM accretion requires increased interorgan exchange of amino acids. Our data suggest that in patients similar to those studied here and during recovery from malnutrition, the degree of change in adjusted REE during refeeding is correlated with change in fat mass and not with change in FFM, and that there is a decrease in oxidation of infused lipids. These mechanisms may contribute to body fat repletion and regulation during weight gain.

Adult↗
PubMed1997

Lipoprotein kinetics in patients with analbuminemia. Evidence for the role of serum albumin in controlling lipoprotein metabolism.

In vitro data suggested that albumin is a key factor controlling apolipoprotein (apo) synthesis by hepatocytes. Studies in analbuminemic rats have shown an increase in secretion of apoB-containing lipoprotein from the liver. We studied the kinetic aspects of apoB- and apoAI-containing lipoprotein metabolism in two sisters with analbuminemia using a constant 14-hour infusion of leucine labeled with stable isotopes. Compared with control subjects, total cholesterol was higher in the two patients (432 and 461 versus 155 +/- 14 mg/dL), as was apoB (257 and 230 versus 72 +/- 7 mg/dL). Triglycerides were slightly increased (134 and 105 versus 89 +/- 9 mg/dL), whereas apoAI was lower (109 and 105 versus 124 +/- 6 mg/dL). VLDL-apoB production was higher, as was the production of IDL-apoB and LDL-apoB (32.8 and 36.0 versus 24.8 +/- 5.9, 32.1 and 27.2 versus 16.4 +/- 2.3, and 14.1 and 17.6 versus 10.3 +/- 1.2 mg.kg-1.d-1, respectively). The fractional catabolic rate of all the apoB-containing lipoproteins was decreased (0.23 and 0.37 versus 0.48 +/- 0.05, 0.27 and 0.28 versus 0.62 +/- 0.08, and 0.012 and 0.009 versus 0.022 +/- 0.002.h-1, respectively). A similar mechanism could explain the dyslipidemia observed in other conditions associated with low albumin levels, such as nephrotic syndrome.

Adult↗
PubMed1997

Glutamine metabolism in very low birth weight infants.

To quantitate glutamine kinetics in premature infants and determine whether glutamine affects leucine metabolism. 11 very low birth weight (< 1250 g) neonates received 4-h i.v. infusions of L-[2H3]leucine and L-[13C5]glutamine, along with orogastric infusion of L-[I-13C]leucine and L-[I-13C]glutamine on the 10th d of life and in the fed state. Patients were receiving parenteral nutrition and were randomized to receive either hypocaloric, enteral preterm formula alone (controls; n = 5), or glutamine (0.2 g.kg-1.d-1 on the day of the study) supplemented formula (GL.n; n = 6). The rates of appearance (Ra) of leucine and glutamine, and their rates of splanchnic extraction were determined from isotopic enrichments in plasma at steady state. Leucine release from protein breakdown did not differ between groups (123 +/- 51 versus 162 +/- 94 mumol.kg-1h-1 in the controls and GLN group, respectively). Glutamine de novo synthesis accounted for > 80% of overall glutamine Ra, and was similar in both groups (626 +/- 177 versus 525 +/- 86 mumol.kg-1.h-1; NS); 46 +/- 16% and 53 +/- 31% of the enteral glutamine underwent first-pass splanchnic extraction in the controls and GLN group, respectively. These findings indicate that the pathways of glutamine de novo synthesis and glutamine utilization in the splanchnic bed are functional in very low birth weight humans by the 10th d of life. Glutamine supplementation provided at low doses on a hypocaloric regimen results in no apparent differences in flux of glutamine or leucine.

Carbon Isotopes↗
PubMed1997

Role of glutamine as a glucose precursor in fasting humans.

Recently, significant incorporation of labeled carbon into plasma glucose was documented during infusion of 14C-labeled glutamine in postabsorptive humans. Such labeling of plasma glucose can occur as a result of two different processes: either 1) through incorporation of glutamine carbon into glucose via glutamine entering Krebs cycle at alpha-ketoglutarate or 2) through simple fixation of labeled CO2 resulting from oxidation of labeled glutamine. Therefore, these studies were designed to determine 1) whether glutamine contributes carbon to gluconeogenesis other than through mere CO2 fixation, and, if so, 2) whether the apparent transfer of carbon from glutamine to glucose increases with fasting. Eight healthy adults were studied on two consecutive days: once after an overnight (18-h) fast and again on the second day of fasting (42-h fast). On each study day, subjects received a simultaneous 5-h infusion of D-[6,6-2H2lglucose, L-[3,4-13C2lglutamine, and L-[1-14C]leucine. Apparent rates of incorporation of glutamine carbon into glucose were estimated from the appearance of 13C into plasma glucose; glucose and glutamine production rates (appearance rate [Ra]) were determined from plasma [2H2]glucose and [13C2]glutamine enrichments, respectively. The appearance of 14C into plasma glucose was used to correct the measured rates of carbon transfer from glutamine to glucose as a result of CO2 fixation. We observed that of the apparent contribution of labeled glutamine to gluconeogenesis, only 4% occurred as a result of fixation of labeled CO2, while 96% seemed to occur through other routes. We also observed that between 18 and 42 h of fasting, 1) the relative contribution of protein breakdown to glutamine production was enhanced, while that of de novo synthesis declined; 2) the apparent contribution of glutamine to glucose production rose from 8 +/- 1 to 16 +/- 3% of overall glucose Ra; and 3) the relative apparent contribution of glutamine to gluconeogenesis remained constant. From the current data, it cannot be ascertained to what extent the apparent carbon transfer from glutamine to glucose represents a true contribution of glutamine to gluconeogenesis or mere carbon exchange between the trichloroacetic acid cycle and the gluconeogenic pathway. These findings are nevertheless compatible with a role of glutamine as a significant precursor of glucose in fasting humans.

Adult↗