Biomedical subjects

C Coudray-Lucas

Publications and source records attributed to C Coudray-Lucas.

At least 37 records · Page 2Linked to original sources

PubMed1997

Amino acid determination in biological fluids by automated ion-exchange chromatography: performance of Hitachi L-8500A.

The Hitachi L-8500A is a newly available apparatus for amino acid (AA) analysis that allows automatic on-line mixing of the ninhydrin reagent. The within-run precision (human plasma pools at three different concentrations) showed CVs < 3.8% except for the lowest concentration of citrulline (4.4%), Tyr (4.5%), and alpha-aminobutyric acid (7.6%), and for the intermediate concentration of Asp (8.7%). Between-run precision (CV) was < 3.1% for 17 AAs and < 8.0% for 24 of 25 AAs (CV Asp = 12.0%). For retention times, within-run precision was < 0.4% and between-run precision < 1.8%. Excellent relations were found between the results from the Hitachi L-8500A and the widely used Beckman 6300 analyzer (0.929 < or = r < or = 0.999). The detection was still linear at 5 mumol/L except for Pro and hydroxyproline (20 mumol/L). The upper limit was at least 2500 mumol/L for 13 AAs and at least 1000 mumol/L for 27 of 29 AAs (anserine = 500, Val = 600 mumol/L). Values from 100 human plasma samples agreed with previously published data. We conclude that the results obtained with the Hitachi L-8500A are satisfactory when compared with those of other AA analyzers utilizing the same method. Furthermore, the Hitachi L-8500A displays several advantages including programming flexibility, microsample capacity, low noise plotting, ammonia filtering, and manual repacking of the analytical column.

Amino Acids↗

PubMed1996

Immunomodulatory effects of ornithine alpha-ketoglutarate in rats with burn injuries.

OBJECTIVE: To investigate the influence of enterally administered ornithine alpha-ketoglutarate (OKG) on muscular amino acid content, eicosanoid release, and polymorphonuclear leukocyte responsiveness after induction of burn injury in rats. DESIGN: Experimental trial. MATERIALS AND METHODS: Four groups of rats were considered: (1) healthy rats that received a standard diet supplemented with 5 g/kg per day of OKG; (2) rats with burn injuries that received the same nutrition as group 1; (3) healthy rats that received standard diet supplemented with glycine in an isonitrogenous amount relative to OKG; and (4) rats with burn injuries that received the same nutrition as group 3. The thymus and 1 skeletal muscle were weighed. The oxidative metabolism of pleural polymorphonuclear leukocytes was measured by means of superoxide generation (O2-) and the chemiluminescent response to opsonized zymosan. Prostaglandin E2 and 6-keto-prostaglandin F1 alpha were measured in the supernatants of pleural and peritoneal cells. RESULTS: The weights of the thymus and the muscle from healthy rats were similar. Those of rats from group 4 were significantly lower (P < .05), whereas those of rats from group 2 were not. Metabolism of OKG led to enhanced amounts of arginine and glutamine in skeletal muscle. The metabolic bursts of polymorphonuclear leukocytes from healthy rats were similar. Those of glycine-treated rats with burn injuries were significantly depressed (P < .05), whereas those of the OKG-treated group were not. Pleural and peritoneal cells from the rats with burn injuries that received OKG generated significantly more prostaglandins (P < .01) than did cells from the other groups of rats. CONCLUSION: Ornithine alpha-ketoglutarate administered to rats with burn injuries displays immunomodulatory properties that can enhance host-defense mechanisms in animals that are affected by a severe injury.

Animals↗

PubMed1996

alpha-Ketoglutarate uptake in human fibroblasts.

Glutamine requirements are increased during injury, in particular to sustain the needs of rapidly growing cells. This includes fibroblasts involved in wound healing. alpha-Ketoglutarate (alpha-KG) has been proved to be a potent precursor of glutamine. However, little is known about the process of its cell uptake. Since this first step could be crucial in alpha-KG metabolism, we have characterized alpha-ketoglutarate uptake in fibroblasts. Total uptake of alpha-ketoglutarate was linear up to 1 mmol and temperature independent. Rate of uptake was independent of the presence of Na+ in the medium. Competition studies with another ketoacid demonstrated the nonspecificity of alpha-ketoglutarate uptake. In addition, 4-hydroxy-alpha-cyanocinnamate, a known inhibitor of anion transport, was ineffective on alpha-ketoglutarate uptake. Taken as a whole, these data provide evidence that alpha-ketoglutarate uptake in fibroblast occurs by an unmediated diffusion process. This suggests that alpha-ketoglutarate uptake is not the controlling step in fibroblasts, i.e. only the availability of extracellular alpha-ketoglutarate. This could be an advantage since during injury, cell membrane depolarization and dissipation of Na+ gradient may limit cellular glutamine uptake.

Amniotic Fluid↗

PubMed1996

Glutamine metabolism and neuropathological disorders in experimental hepatic encephalopathy: effect of transplanted hepatocytes.

BACKGROUND: Physiopathology of hepatic encephalopathy remains unclear. Recent studies have suggested that ammonia would not act by itself but through an increase in glutamine in the brain. We have previously demonstrated that transplantation of syngeneic hepatocytes into the spleen was able to correct both behavioral deficits and plasma amino acid changes observed in portacaval shunted rats. The aim of the present work was to show a correlation between the correction of chronic hepatic encephalopathy by means of intrasplenic hepatocyte transplantation and two parameters, brain glutamine concentration and ultrastructural aspects of astrocytes. METHODS: Inbred male Wistar Furth rats were divided into three groups: sham-operated rats (n = 10), rats subjected to portacaval shunt (n = 10), and rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10). Chronic hepatic encephalopathy was quantified 30 and 60 days after operation by means of nose-poke exploration and spontaneous activity. Pathologic examination and measurement of glutamine concentrations in the corpus striatus and in the cerebral cortex were performed 60 days after operation. RESULTS: Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. After portacaval shunt a significant glutamine increase occurred in the corpus striatus and in the cerebral cortex when compared with sham rats (p < 0.05). Ultrastructural examination showed modification of astrocytes named Alzheimer type II after portacaval shunt. Correction of behavioral abnormalities by means of intrasplenic hepatocyte transplantation was associated with partial correction of striatal glutamine increase and with decrease in astrocyte alterations. Cortex glutamine concentration in portacaval shunt-intrasplenic hepatocyte transplantation group and in portacaval shunt rats did not differ significantly. CONCLUSIONS: These data show that intrasplenic hepatocyte transplantation not only prevents neurologic disorders of hepatic encephalopathy but can also decrease glutamine and ultrastructural alterations in the corpus striatus in an experimental model of chronic liver failure. These data are in favor of the involvement of glutamine in chronic hepatic encephalopathy. These results suggest that intrasplenic hepatocyte transplantation might be of therapeutic interest in chronic liver failure.

Animals↗

PubMed1996

Ornithine alpha-ketoglutarate counteracts thymus involution and glutamine depletion in endotoxemic rats.

This work studied the action of ornithine a-ketoglutarate (OKG) supplementation in an experimental model of endotoxemia in the rat. Male Wistar rats were injected intraperitoneally with lipopolysaccharide (LPS) from Escherichia coli (0127:B8). They were fasted for 24 h, then refed for 48 h with an enteral diet supplemented with either OKG (66 mg N x kg(-1) x d(-1)) or glycine, isonitrogenous to the OKG group. A control (sham) group was also studied. LPS treatment induced a decrease in thymus and muscle weights compared to controls, and a decrease in glutamine and arginine concentrations in the anterior tibialis muscle. Supplementation with OKG restored thymus weight and muscle arginine level and increased muscle glutamine concentration, when compared to controls. We conclude that OKG counteracts the thymic involution that occurs with endotoxemia, and restores the muscular content of glutamine and arginine, both of which are involved in the regulation of immune function.

Journal Article↗

PubMed1996

[Reference intervals and biological profile in a group of healthy elderly population in the Paris region].

The superimposition of pathological processes on ageing-related metabolic changes makes the interpretation of laboratory data difficult in the elderly. Therefore, in order to establish reference values of anthropometric, hematological and biochemical variables, we have carefully selected fit, health-conscious elderly subjects on the basis of clinical and biological criteria. We observed a trend for a wider range of values than in young adults. For some variables, the values were shifted down (eg: albumin, vitamin D) or up (eg: glucose, urea, cholesterol, ferritin), as a result of slow metabolic changes or progressive functional decline of different organs. The high prevalence of hypovitaminosis D was worthy of note, particularly in women, suggesting a high risk of deficiency.

Aged↗

PubMed1995

Glucose contribution to nucleic acid base synthesis in proliferating hepatoma cells: a glycine-biosynthesis-mediated pathway.

The coupling of glycolysis to serine and glycine metabolism was studied in fast-growing Zajdela hepatoma cultured cells. During the exponential phase of growth, occurring between 12 and 72 h, cells exhibited a decreased glycogen content together with a high glycolytic activity. Glycogen labelling, evaluated by 1 h-pulse experiments with [U-14C]glucose (5.5 mM), was minimal during the first 48 h and increased 2.5-fold at 72 h and 8-fold at 96 h, at which times it was also stimulated 2-fold by 10 nM insulin. [U-14C]Glucose carbons were incorporated into nucleic acid bases, with maximal incorporation at 72 h, the rate of nucleotide base labelling exceeding that of glycogen during the first 2 days of culture. Incubation of the cells with [U-14C]glucose resulted in the release into the medium of 14C-labelled glycine, the first intermediate formed on the route from serine to DNA. The rate of release per cell decreased as a function of cell growth, concomitantly with an increased rate of glucose carbon incorporation into nucleotide bases. The latter implied the intermediary formation of amino acids since the transaminase inhibitor cycloserine (10 mM), which totally inhibited [14C]glycine release, decreased by 65% nucleotide labelling from [U-14C]glucose. A dose-dependent inhibition by serine of the rate of [U-14C]glucose carbon incorporation into nucleotide bases was observed, which was maximal at 5 mM serine. These metabolic flux measurements indicate that glucose can be used as a precursor of nucleic acid synthesis. These results strongly suggest that this process is to a large extent mediated by a serine/glycine-biosynthesis-mediated pathway, and reinforce the hypothesis that glycolysis contributes to enhancing the provision of precursors required for cell proliferation.

Animals↗

PubMed1995

Metabolism of ornithine, alpha-ketoglutarate and arginine in isolated perfused rat liver.

Ornithine (Orn; alpha-ketoglutarate (alpha KG) salt) and arginine (Arg) supplementation of enteral diets has been advocated in the treatment of hypercatabolism of trauma patients, but both compounds are subject to extensive hepatic metabolism. To compare the metabolism of these two compounds and to evaluate the possible influence of the alpha KG moiety, livers were perfused with alpha KG, Orn, ornithine alpha-ketoglutarate (OKG) or Arg (n 6 in each group) for 1 h. Arg uptake was nearly fourfold higher than Orn uptake (690 (SD 162) v. 178 (SD 30) nmol/min per g liver), and Orn uptake was not modified by alpha KG. Orn was totally metabolized by the liver, whereas Arg led to Orn release (408 (SD 159) nmol/min per g liver) and a threefold stimulation of urea production (Arg 1.44 (SD 0.22) v. Orn 0.45 (SD 0.09) mumol/min per g liver). alpha KG alone only increased hepatic aspartate uptake but, when associated with Orn as OKG, it led to an increase in glutamate release and in proline content in the liver and to a decrease in proline uptake. From these findings we conclude that (1) Arg load is extensively metabolized by the liver, inducing urea production, (2) in enteral use, Orn supplementation appears preferable to Arg as it is less ureogenic (as also recently demonstrated in vivo in stressed rats receiving isomolar amounts of Arg and Orn), (3) the liver participates in the Orn-alpha KG metabolic interaction, mostly in proline metabolism, which occurs in the splanchnic area.

Animals↗

PubMed1994

Biochemical assessment of nutritional status in patients with chronic obstructive pulmonary disease and acute respiratory failure on admission to an intensive care unit.

Although chronic obstructive pulmonary disease (COPD) is associated with weight loss and malnutrition, there is a paucity of relevant data on COPD patients with acute respiratory failure (ARF). We studied 30 consecutive patients on the day of admission to our intensive care unit for ARF. In addition to a clinical work-up, the following biochemical parameters were determined: markers of nutritional status (albumin - ALB, transferrin - TRF, transthyretin - TTR, retinol binding protein - RBP, fibronectin), inflammation (C-reactive protein - CRP, alpha(1) glycoprotein acid - alpha(1)GPA) and catabolism (plasma phenylalanine - PHE, urinary 3-methylhistidine - 3-MH). Values were expressed as mean +/- SD and compared to those of 10 healthy subjects matched for age. COPD-ARF patients had a poor protein status (ALB = 30 +/- 5 vs 42 +/- 3 g.l(-1); TTR = 118 +/- 75 vs 251 +/- 43 mg.l(-1); RBP = 23 +/- 12 vs 46 +/- 8 mg.l(-1); p < 0.001), were hypercatabolic (3-MH Cr = 31 +/- 12 vs 22 +/- 7 mumol.mmol Cr (-1); PHE = 62 +/- 27 vs 46 +/- 10 mumol.l(-1); p < 0.001) and inflamed (CRP = 68 +/- 50 vs 12 +/- 5 mg.l(-1); alpha(1)GPA = 1.2 +/- 0.4 vs 0.5 +/- 0.1 g.l(-1); p < 0.001). Severity of the disease correlated with short half-life proteins and protein catabolism markers but not with inflammation markers. Considering ALB, TTR, RBP, the 3- MH Cr ratio and PHE values, the 30 COPD patients fell into 3 groups: chronic malnutrition (n = 7), acute malnutrition (n = 2), and acute + chronic malnutrition (n = 18). 3 patients had normal nutritional status. We conclude that an assessment of nutritional status at admission to intensive care units could contribute towards a rapid formulation of specific nutritional therapy.

Journal Article↗

PubMed1994

Extensive laboratory assessment of nutritional status in fit, health-conscious, elderly people living in the Paris area. Research Group on Aging.

OBJECTIVE: Nutritional status-related biological indexes were measured in fit, health-conscious elderly subjects in order to establish reference values for people over 70 years. SUBJECTS: 103 men and 90 women aged 70-89 years living freely in the Paris area volunteered to participate. METHODS: Nutritional status was assessed by anthropometric and biochemical methods. RESULTS: Serum protein and amino acid status was similar to that of young adults, with only 5.2% of the elderly subjects showing transthyretin concentrations < 0.20 g/L, as well as decreased essential amino acid levels. Iron status, assessed in terms of serum and erythrocyte ferritin levels, total iron binding capacity and erythrocyte protoporphyrin tended to be satisfactory, but iron depletion was detected in 8.8% of the subjects. Serum ferritin levels were elevated in 19.7% of the subjects. Folate and vitamin B12 status was satisfactory, while hypovitaminosis D was observed in 48.2% of cases. CONCLUSION: Our findings suggest that, in aging uncomplicated by disease, nutritional status is similar to that in younger adults, although the range of values tended to be wider, with a higher risk of certain nutrient deficiencies.

Aged↗

PubMed1994

Assessment of the carbon tetrachloride-induced cirrhosis model for studies of nitrogen metabolism in chronic liver disease.

We evaluated the rat cirrhosis model obtained by repeated intraperitoneal administration of CCl4 (group C) with regard to biological and nutritional conditions in comparison to ad libitum (group AL) and pair-fed control rats. Cirrhotic rats were divided into two groups according to their clinical condition: group C1 (n = 4) represented those in good physical condition and group C2 those (n = 10) in poor physical condition. Autopsy indicated that rats in group C2 suffered from severe malnutrition as judged by body weight, carcass weight and the carcass/body weight ratio. However, all 14 treated rats presented the same micronodular cirrhosis and the same alterations in liver function, except for alkaline phosphatase activity (group C1: 110 +/- 63 IU/l, group C2: 259 +/- 110 IU/l; p < 0.05). In the cirrhosis groups, plasma levels of branched-chain amino acids (BCAA) and the BCAA/aromatic amino acid (AAA) ratio were significantly reduced, but values in groups C1 and C2 were not significantly different (BCAA/AAA: 1.9 +/- 0.9 in group C1, 1.5 +/- 0.8 in group C2, 2.8 +/- 0.3 in group AL; C1 and C2, vs. AL: p < 0.05). These alterations were similar to those observed in human cirrhosis and were not solely the result of reduced food intake, as indicated by the lack of difference between pair-fed and ad libitum-fed control rats.

Amino Acids↗

PubMed1993

[Enteral nutrition in patients with chronic obstructive bronchopathy treated by artificial ventilation. Effect of conventional feeding on anthropometric and biochemical parameters].

The influence of conventional gastric tube feeding on anthropometric and biochemical parameters was studied prospectively during 12 months in 14 patients with chronic obstructive lung disease put on mechanical ventilation for respiratory failure. The anthropometric parameters were: body weight, tricipital skin fold, brachial and brachial muscle circumferences. The biochemical parameters included albumin, transferrin, retinol binding protein, transthyretin, acid alpha-1-glycoprotein, C-reactive protein, fibronectin and amino acids in blood, and 3-methylhistidine in urine. Measurements were performed on inclusion, then every 3 days until D15. After 15 days of a nutrition bringing 28.8 +/- 8.9 calories/kg/day and 13.9 +/- 2.2 grams of nitrogen per day, no improvement in anthropometric parameters was observed. On D0, comparisons with healthy controls showed that visceral serum proteins levels were significantly lower and inflammatory proteins levels significantly higher (P < 0.05); the levels of protein metabolism markers were higher, but not significantly, and those of the principal glucose-forming amino acids were significantly lower (P < 0.01). On D15, comparisons with the initial values showed that the values of retinol binding protein and transthyretin were increased (P < 0.05 and 0.01 respectively), whereas the values of the other visceral proteins were little modified; yet their concentrations remained significantly lower than those found in controls, except for the retinol binding protein. Inflammatory proteins levels were high, with a significant (P = 0.05) difference for the acid alpha-1-glycoprotein, and the patients remained in slight catabolism while their nitrogen balance was positive. These results should encourage to carry out studies on the qualitative composition of artificial nutrition in order to optimize its effectiveness in the treatment of these patients.

Aged↗

PubMed1992

Intrasplenic hepatocellular transplantation corrects hepatic encephalopathy in portacaval-shunted rats.

The aim of this work was to evaluate the effect of intrasplenic hepatocellular transplantation on hepatic encephalopathy in an experimental model of chronic liver failure induced by end-to-side portacaval shunt in the rat. Inbred male Wistar Furth rats were divided into three groups: rats subjected to portacaval shunt (n = 10), rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10) and sham-operated rats (n = 10). Behavior tests were performed in a blind fashion at 3 wk, at 2 mo and at 3 mo after surgery. Spontaneous activity and nose-poke exploration by individual rats were studied in automated open field boxes equipped with infrared cells. Each cell beam interruption was automatically recorded on a microcomputer and transformed into a score index (counts/hour). Plasma levels of amino acids, ammonia and total biliary acids were measured. Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. Intrasplenic hepatocellular transplantation significantly increased spontaneous activity after 2 mo and improved nose-poke exploration after 3 wk. At 3 mo, spontaneous activity and nose-poke exploration in portacaval shunt/intrasplenic hepatocellular transplantation rats were not significantly different from those of sham rats. Increases in plasma ammonia levels after portacaval shunt were not corrected. Amino acid imbalance and bile acid concentration in plasma were partially corrected by intrasplenic hepatocellular transplantation. These data show that intrasplenic hepatocellular transplantation can correct the neurological symptoms of hepatic encephalopathy in an experimental model of chronic liver failure and suggest that intrasplenic hepatocellular transplantation might be of therapeutic interest in chronic liver failure.

Animals↗

PubMed1992

Branched-chain amino acid metabolism in isolated perfused liver of cirrhotic rats.

We examined the possible contribution of the liver to the alterations in branched-chain amino acid (BCAA) metabolism in cirrhosis. The livers of male Sprague-Dawley rats with CCl4-induced cirrhosis were removed and placed in a recirculating perfusion system. Net amino acid uptake and release were determined over 55 min. Results were compared with those obtained with control animals, which were either pair-fed or fed ad libitum. Intrahepatic amino acid concentrations were determined at the end of the perfusion. The release of isoleucine and leucine was significantly lower in the cirrhotic livers than in the controls fed ad libitum. There was no difference between the cirrhotic and pair-fed groups with regard to the fluxes of the three BCAA. Intrahepatic concentrations of BCAA were reduced only in pair-fed controls. These results suggest that both cirrhosis and a low protein/calorie diet alter hepatic BCAA flux, but via different mechanisms. In cirrhosis, alterations could be due both to low food intake and to BCAA metabolism in non-parenchymal cells.

Amino Acids, Branched-Chain↗

PubMed1992

[Effects of fatty acids on hepatic amino acid metabolism in isolated perfused liver in rats].

Large disparity in experimental conditions concerning the use of isolated perfused liver led us to investigate the effects of two free-fatty acids on amino acid metabolism in this model. Oleate uptake was 210 +/- 46 nmol/min.g and octanoate uptake 550 +/- 60 nmol/min.g. Fatty acid utilization led to an increase in ketogenesis, enhanced by octanoate in accordance with its known availability for beta-oxidation. In our experiments neither oleate nor octanoate modified hepatic amino acid exchange and metabolism as assessed by the measurements of amino acids fluxes and glucose and urea production.

Amino Acids↗

PubMed1990

Action of ornithine alpha ketoglutarate on DNA synthesis by human fibroblasts.

Ornithine alpha ketoglutarate (OKG) is largely used in clinical nutrition for its anabolic effects. However, the mechanism of its action remains questionable. We investigated the effect of OKG on the rate of DNA synthesis in human fibroblasts. The in vitro experimental procedure required to demonstrate in cell culture the anabolic effects of OKG observed in vivo was found to be glutamine-free and serum-poor medium with sparse cells. In these conditions, OKG induced a significant increase in [3H]thymidine incorporation compared to untreated control cells. This effect was dose-dependent and was observed in all the cultures tested. Taken individually, the two constituents of OKG, i.e. alpha KG and Orn, also showed a stimulatory effect, but did not demonstrate a dose-dependent response. Concomitant analysis of extracellular aminoacids showed in alpha KG-treated cultures an increase in glutamate and a decrease in aspartate, suggesting a cellular transamination of alpha KG. Glutamine, which is the preferential energetic substrate of fibroblasts, can be produced from glutamate and might play a role in the action of OKG. Moreover, OKG induced a rise in the cellular polyamine content. This, in association with the inhibitory effect on OKG action of difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, suggests a link between the polyamine biosynthesis pathway and the anabolic effect of OKG.

Cells, Cultured↗

PubMed1990

Amino acid metabolism in isolated perfused rat liver.

Conflicting evidence concerning hepatic amino acid (AA) metabolism in the isolated perfused rat liver (IPRL) led us to investigate the response of IPRL using perfusates with various AA contents. Perfusion (n = 4) with whole rat blood diluted in Krebs buffer (1:3, v/v) led to acute proteolysis on account of AA deprivation, as shown by the large release of AA (approximately 1400 mumoles in 120 min), especially branched-chain AA (BCAA) (e.g., Leu, 35.4 +/- 10.4 nmole.min-1.g-1 the first hour, 34.3 +/- 5.5 nmole.min-1.g-1 the second hour). In a first attempt to prevent proteolysis, livers (n = 4) were perfused with the previous medium supplemented with AA known for their antiproteolytic activity, at twice their physiological concentrations. Results during the first hour showed uptake of several AA (mainly alanine, glutamine, and proline), reduced release of BCAA (leucine, 12.5 +/- 6.3 nmole.min-1.g-1), and an increase in glucose and urea production. However, during the second hour, because of the use of a recirculating system, progressive AA depletion induced a reappearance of proteolysis. A two-step AA loading technique, i.e., the addition of antiproteolytic AA at the beginning of the perfusion and the addition of a balanced AA mixture at 60 min caused a further decrease in proteolysis during the 2 hr of perfusion (n = 6). Under these conditions, most AA were taken up by the liver with uptake values comparable to those observed in vivo.

Amino Acids↗

PubMed1990

Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects.

Ornithine alpha-ketoglutarate (OKG) has been useful as an adjuvant of enteral and parenteral nutrition. However, its metabolism and mechanism of action remain unclear although it is known that alpha-ketoglutarate (alpha KG) and ornithine (ORN) follow, in part, common metabolic pathways. Six fasting healthy male subjects underwent three separate oral load tests: (i) they received 10 g of OKG (i.e., 3.6 g of alpha KG and 6.4 g of ORN); (ii) 6.4 g of ORN as ornithine hydrochloride, and (iii) 3.6 g of alpha KG as calcium alpha-ketoglutarate. Blood was drawn 15 times over a five-hour period for measurements of plasma amino acids, alpha KG, insulin, and glucagon. After OKG and ORN administration, plasma ORN peaked at 60-75 min (494 +/- 91 and 541 +/- 85 mumol/L). The increase in plasma alpha KG was very small. OKG, alpha KG, and ORN all increased glutamate concentrations at 60 min (mean: +43%, +68%, +68%, respectively, p less than 0.05 compared to basal values). However, only OKG increased proline and arginine levels at 60 min (mean: +35%, p less than 0.01 and mean: +41%, p less than 0.05). Furthermore, glutamate, proline, and arginine concentrations correlated linearly with ornithine levels at 60 min. Finally, OKG increased insulinemia and glucagonemia (mean: +24% at 15 min, p less than 0.05 and +30% at 60 min, p less than 0.01, respectively). These data provide evidence that the combination of ORN and alpha KG modifies amino acid metabolism in a way which is not observed when they are administered separately. In addition, the OKG-mediated increase in insulin levels probably does not appear to result from a direct action of ORN on pancreatic secretion.

Administration, Oral↗