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PubMed1990

[The parenchymatous-stromal interrelationships in adenocarcinomas of the large intestine (an electron radioautographic study)].

Parenchymatous and stromal cells in colonic adenocarcinomas were studied electron-radiographically. The properties of the nucleic acid and protein synthesis in the cylindrical and goblet cells in carcinoma (partial 3H-thymidine incorporation, heterogeneity of 3H-uridine and amino acid mixture incorporation) indicate a relatively low level of their differentiation, lower degree of their participation in a specific function, retaining their capacity to proliferate. A high number of 3H-thymidine-labelled stem cells which are the main source of tumour growth is observed in carcinoma. Stroma in carcinoma is characterized by endotheliocyte and fibroblast proliferation (3H-thymidine incorporation), high degree of metabolic processes in some of these cells (3H-uridine and amino acid mixture incorporation) and by the disturbance of immunocompetent cell specific function (partial and weak labelling of the immunocompetent cells with 3H-uridine and amino acid mixture).

Adenocarcinoma↗

PubMed1981

Amino acid solutions: composition and suitability for intravenous feeding in infants.

The amino acid composition, the electrolyte content, the titratable acidity, the osmolality and the pH of nine crystalline amino acid mixtures and one protein hydrolysate was analyzed and the results were compared with the data provided by the manufacturer. The amino acid composition of the protein hydrolysate (Aminosol 10%) showed a marked discrepancy between the concentration of amino acids measured and the concentration given by the manufacturer. The sodium, chloride and especially the ammonia content is high as compared to the synthetic amino acid solutions. The amino acid composition of the crystalline amino acid solutions was generally in reasonable good agreement with the composition given by the manufacturers. In DL-Trophysan an unknown amino acid, probably alloisoleucine, was found. Only in two (Vamin 7% and Amino acid solution 4200) out of eleven crystalline amino acid mixtures cystine and tyrosine could be detected; therefore only Amino acid solution 4200 and Vamin 7% might be suited for infants. However, infants fed parenterally with Vamin 7% often showed elevated levels of several amino acids. Amino acid solution 4200 with a composition similar to human milk seems to be more adapted and needs further investigation.

Amino Acids↗

PubMed1991

Effect of a cholecystokinin antagonist on meal-stimulated insulin and pancreatic polypeptide release in humans.

A cholecystokinin (CCK) receptor antagonist, loxiglumide, was used to investigate the potential regulating role of CCK in the entero-insular axis in humans. Ingestion of a mixed liquid meal stimulated plasma CCK, insulin, and pancreatic polypeptide (PP) release in the control experiment. With iv loxiglumide (22 mumol/kg.h), mean plasma insulin and glucose levels did not differ between placebo and loxiglumide treatment. The area under the plasma concentration for PP was reduced to 6,060 +/- 1,706 (P less than 0.05) compared to that during placebo treatment (12,266 +/- 4,748). Administration of loxiglumide failed to change insulin secretion in response to perfusion of the same meal or perfusion of a 10-amino acid solution into the duodenum. However, PP secretion in response to the intraduodenal meal or amino acid mixture was abolished after loxiglumide (P less than 0.05). Intravenous administration of the 10-amino acid mixture stimulated insulin from a mean basal level of 7 +/- 3 microU/mL to a peak level of 16 +/- 4 microU/mL. Infusion of a CCK octapeptide (CCK-8) at 8.6 pmol/kg.h, which produced a plasma concentration of 3.3 pmol/L, which is within the postprandial range, augmented amino acid-stimulated insulin and PP output (P less than 0.05). When CCK-8 was infused with loxiglumide, the insulin and PP responses were similar to the values found with loxiglumide alone. We conclude that CCK receptor blockade with iv loxiglumide does not affect postprandial insulin secretion. CCK is, therefore, not a major incretin. However, it is involved in the postprandial PP response, especially during the intestinal phase stimulation. These data suggest that CCK has a role in the human enteroinsular axis.

Adult↗

PubMed1976

Regulatory role of dietary leucine on plasma branched-chain amino acid levels in young men.

Four healthy young men were studied to explore the effects of dietary leucine intake on plasma levels of leucine,isoleucine and valine. Leucine-, valine-, leucine-valine-, and leucine-isoleucine-valine-free amino acid mixtures were studied during four-day experimental diet periods. The effects of giving amino acid mixtures with high-carbohydrate, low-fat or low-carbohydrate, high-fat diets were also studied. Deficient leucine intake increased plasma levels of valine and isoleucine, but a valine-free diet did not affect plasma levels of the other branched-chain amino acids. Leucine influence was evident during the postprandial and fasted phases. Valine and isoleucine levels were less markedly reduced when diets devoid of these amino acids were also leucine-free, as compared with a diet providing adequate leucine. Changes in the major dietary energy source failed to influence the qualitative effects of dietary leucine adequacy on the branched-chain amino acid levels in plasma. The results suggest that leucine facilitates both tissue uptake of branched-chain amino acids and their intracellular metabolism.

Adolescent↗

PubMed1984

Influence of basic and branched chain amino acid interactions on the lysine and valine requirements of young turkeys.

Two experiments were conducted to determine the influence of amino acid interactions on the lysine and valine adequacy of a low protein diet fed to Large White turkeys from 7 to 19 days of age. Corn-soybean meal diets containing 22 and 30% protein served as controls in both experiments. Test diets involved supplementation of the 22% protein diet with several essential amino acid mixtures. Each diet was fed ad libitum to two pens of eight males and two pens of eight females in each of three trials, except that the 22% protein control diet was fed to four and two pens of each sex per trial in Experiments 1 and 2, respectively. Experiment 1 varied the levels of lysine (0, .60, and 1.20%) and arginine (0, .64, and 1.28%) included in the amino acid mixture. A decrease in supplemental lysine from .60 to 0% reduced weight gain and feed efficiency by 8.6 and 2.4%, respectively. The lysine deficiency was not exacerbated by arginine supplementation up to 179% of the requirement. The effects of altering the leucine (0, .54, and 1.08%) and isoleucine (0 and .4%) contents of the amino acid mixture on the valine requirement were investigated in Experiment 2. Leucine and isoleucine supplementation of diets containing 1.25% valine acted independently to reduce weight gain and feed intake, but the depressions were reversed with the addition of .44% valine. Maximum weight gain and feed efficiency were not achieved with diets containing 1.25% valine and no added leucine or isoleucine, which were indicative of a true valine deficiency in the basal 22% protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMedDate not supplied

[Role of the thyroid gland in the effects of parenteral feeding].

In 82 albino rats with experimental thyrotoxicosis the assimilation of parenterally administered amino acid mixture of mori-amine S-2 was investigation. In thyrotoxicosis the assimilation of the amino acid mixture was found to be down. It is only a combination of mori-amine S-2 with vitamins, hormones and 6-methyluracil that facilitates the utilization of free amino acids by the tissues (this being borne out by a falling level of aminic nitrogen in the blood, skeletal muscles, heart and liver), persistently upholds the positive nitrous balance, prevents losses of the body weight and foces down oxygen consumption.

Amino Acids↗

PubMed2004

A signaling role of glutamine in insulin secretion.

Children with hypoglycemia due to recessive loss of function mutations of the beta-cell ATP-sensitive potassium (K(ATP)) channel can develop hypoglycemia in response to protein feeding. We hypothesized that amino acids might stimulate insulin secretion by unknown mechanisms, because the K(ATP) channel-dependent pathway of insulin secretion is defective. We therefore investigated the effects of amino acids on insulin secretion and intracellular calcium in islets from normal and sulfonylurea receptor 1 knockout (SUR1-/-) mice. Even though SUR1-/- mice are euglycemic, their islets are considered a suitable model for studies of the human genetic defect. SUR1-/- islets, but not normal islets, released insulin in response to an amino acid mixture ramp. This response to amino acids was decreased by 60% when glutamine was omitted. Insulin release by SUR1-/- islets was also stimulated by a ramp of glutamine alone. Glutamine was more potent than leucine or dimethyl glutamate. Basal intracellular calcium was elevated in SUR1-/- islets and was increased further by glutamine. In normal islets, methionine sulfoximine, a glutamine synthetase inhibitor, suppressed insulin release in response to a glucose ramp. This inhibition was reversed by glutamine or by 6-diazo-5-oxo-l-norleucine, a non-metabolizable glutamine analogue. High glucose doubled glutamine levels of islets. Methionine sulfoximine inhibition of glucose stimulated insulin secretion was associated with accumulation of glutamate and aspartate. We hypothesize that glutamine plays a critical role as a signaling molecule in amino acid- and glucose-stimulated insulin secretion, and that beta-cell depolarization and subsequent intracellular calcium elevation are required for this glutamine effect to occur.

ATP-Binding Cassette Transporters↗

PubMed1991

Changes in whole body and tissue oxygen consumption during recovery from hypothermia: effect of amino acid infusion.

OBJECTIVE: To study the effects of amino acids on whole body and peripheral energy metabolism during recovery from post-operative hypothermia. DESIGN: Clinical study using three randomly assigned patient groups. SETTING: ICU of a university hospital. PATIENTS: Nineteen elective coronary bypass operation patients. INTERVENTIONS: Postoperatively, either glucose alone, glucose and a conventional amino acid solution, or glucose and a branch-chain amino acid enriched solution was infused. After ICU arrival (period 1) both conventional amino acid solution and branch-chain amino acid enriched solution groups received 0.15 g/kg-day of nitrogen as a conventional amino acid mixture (20% branch-chain amino acids). After rewarming (period 2), both groups received 0.18 g of nitrogen/kg-day for 2 hrs (branch-chain amino acid content 20% in the conventional amino acid solution and 35% in the branch-chain amino acid enriched solution), and for the following 2 hrs (period 3), 0.22 g of nitrogen/kg-day (branch-chain amino acid content 20% in the conventional amino acid solution and 50% in the branch-chain amino acid enriched solution). MEASUREMENTS AND MAIN RESULTS: Whole body oxygen consumption (VO2) increased during period 1 and continued to increase during period 2 (baseline, 133 +/- 20 mL/min.m2; period 1, 152 +/- 12 mL/min.m2; period 2, 158 +/- 21 mL/min.m2; period 3, 153 +/- 15 mL/min.m2; p less than .05, period 1 vs. baseline). VO2 in the leg increased during period 1 but remained constant thereafter (baseline, 16 +/- 8 mL/min.m2; period 1, 26 +/- 14 mL/min.m2; period 2, 23 +/- 6 mL/min.m2; period 3, 24 +/- 10 mL/min.m2; p less than .05, period 1 vs. baseline). Amino acid infusions had no thermogenic effect. A two-phase redistribution of VO2 and leg VO2 suggested increased visceral VO2 after rewarming. CONCLUSION: The amino acid infusions had no effect on the leg uptake of glucose, ketone bodies, and pyruvate and the leg release of lactate, free fatty acids, and triglycerides, which remained constant during the study.

Adult↗

PubMed1961

Utilization of sulfur compounds by Streptococcus bovis.

Prescott, J. M. (A. &. M. College of Texas, College Station). Utilization of sulfur compounds by Streptococcus bovis. J. Bacteriol. 82:724-728. 1961.-Two strains of Streptococcus bovis utilize a variety of compounds as their only source of sulfur, yet exert a definite selectivity in their nutritional requirements for this element. Among sulfur-containing amino acids and related compounds, cystine and cysteine support excellent growth, but cysteic acid and cysteine sulfinic acid do not; methionine is completely inactive as an only sulfur source, but growth is provided by lanthionine, djenkolic acid, allo-cystathionine, homocystine, homocysteine, and glutathione. Several organic sulfur compounds other than amino acids are effective sulfur sources, among which are thioglycolate, thiomalate, thiourea, and thiouracil. In contrast, thiodiglycolate, thiodiglycol, and (phenylthio) acetic acid fail to support growth. Of the inorganic sulfur sources tested, sulfide and thiosulfate are utilized, but sulfite and sulfate are not; it thus appears that the state of oxidation is a critical factor in the utilization of sulfur by these strains of S. bovis. A complex amino acid mixture, without sulfur-containing amino acids, produces more rapid and reproducible growth than either arginine or ammonium acetate when used as a nitrogen source for testing the sulfur compounds. Growth rates are frequently better when the sulfur sources are autoclaved than when they are sterilized by filtration, although the qualitative responses to the compounds are generally similar.

Alanine↗

PubMed2003

Reciprocal inhibition of umbilical uptake within groups of amino acids.

Eight pregnant sheep were infused with two amino acid mixtures of different composition: essential amino acids only and the essentials plus some of the nonessentials. Uterine and umbilical uptakes of amino acids were measured before and during infusion. For most of the amino acids, the infusion increased both maternal plasma concentration and umbilical uptake. However, depending on the infusate composition, the increase in maternal concentration of some amino acids was associated with no change or a significant reduction in umbilical uptake. Data were pooled from this and other, similar studies to test the hypothesis that umbilical uptake of several amino acids can be inhibited by coinfused amino acids. The test consisted of fitting the data, by means of multiple regression analysis, to the linear transformation of a saturation kinetics equation in which uptake is assumed to depend on maternal arterial concentrations. The analysis showed significant inhibitory effects within the neutral essential amino acids group and within the lysine-arginine group, with no demonstrable interaction between the two groups. Uterine uptakes did not show clear evidence of saturability and inhibitory interactions, suggesting a large transport capacity and low transporter affinity on the maternal surface of the trophoblast. We conclude that the transport of any given amino acid from placenta to fetus is a function of both its own maternal concentration and the maternal concentration of inhibitory amino acids.

Amino Acids↗

PubMed1990

Intravenous amino acids stimulate human gallbladder emptying and hormone release.

Gallbladder stasis during prolonged total parenteral nutrition (TPN) has been documented. We have examined the effect of intravenous amino acid infusion on human gallbladder contraction and release of cholecystokinin (CCK). Five healthy adult volunteers were given amino acid infusions at different rates (65, 125, 240, and 600 mg.kg-1.h-1). The volume of the gallbladder was calculated by means of ultrasonographic measurements. Plasma samples were analyzed for CCK immunoreactivity. Gallbladder and hormone responses after intravenous amino acids were compared with responses after a fat meal, after a protein meal, and after ingestion of an oral amino acid mixture. We found that intravenous amino acids stimulated human gallbladder contraction in a dose-related manner. The mechanism of stimulation may be through the release of CCK although significant correlation was not demonstrated. The magnitude of response is similar to that seen after meal stimulation. To compare the delivery of amino acids during a standard meal and during each dose of intravenous amino acids, peripheral plasma levels of dietary amino acids were measured after a standard commercially prepared enteral supplement meal and after each dose of intravenous amino acids. Our lower doses of amino acid infused resulted in levels of circulating amino acid comparable to those after a meal. The induction of gallbladder contraction and release of CCK in human recipients of parenteral nutrition may be of value in some circumstances.

Adult↗

PubMed1990

Cell volume regulatory responses of isolated perfused rat liver. The effect of amino acids.

1) Addition of glutamine, glycine, alanine, serine, phenylalanine, proline at a concentration of 3mM, each, or of an amino-acid mixture resembling the physiological amino-acid composition of portal venous blood, to influent perfusate of isolated perfused rat liver led to a 4-6% increase of liver mass without increase of the [3H]inulin space, and biphasic K+ movements across the plasma membrane. These K+ movements consisted of an initial net K+ uptake (0.4-0.9 mumol X g-1 liver) for about 2 min, being followed by a net K+ release (1.0-2.8 mumol X g-1 liver) during the next 10 min. Withdrawal of the amino acids from influent perfusate caused a slow net K+ reuptake by the liver and restored the initial liver mass. No effects on liver mass and K+ fluxes were observed following addition of glutamate or glucose at a concentration of 3mM, each. 2) Aminooxyacetate did not affect the alanine (3 mM) induced increase in liver mass. However, in presence of aminooxyacetate the alanine-induced net K+ release from the liver (i.e. K+ release from 2-10 min minus initial K+ uptake) increased from 0.1 to 2.2 mumol X g-1 liver, whereby simultaneously the alanine tissue level rose from 6.8 to 13.3 mumol X g-1 (corresponding to an increase of the intracellular alanine concentration from about 12 to 25 mM) in presence of aminooxyacetate. 3) When livers were perfused with different glutamine concentrations, a maximal increase in liver mass of 5-6% was observed at glutamine concentrations above 1.5-2mM. A halfmaximal increase in liver mass was observed at 0.6-1.0mM glutamine in influent, i.e. at the physiological portal glutamine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed2005

Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability.

To examine the molecular mechanisms by which plasma amino acid elevation impairs insulin action, we studied seven healthy men twice in random order during infusion of an amino acid mixture or saline (total plasma amino acid approximately 6 vs. approximately 2 mmol/l). Somatostatin-insulin-glucose clamps created conditions of low peripheral hyperinsulinemia ( approximately 100 pmol/l, 0-180 min) and prandial-like peripheral hyperinsulinemia ( approximately 430 pmol/l, 180-360 min). At low peripheral hyperinsulinemia, endogenous glucose production (EGP) did not change during amino acid infusion but decreased by approximately 70% during saline infusion (EGP(150-180 min) 11 +/- 1 vs. 3 +/- 1 mumol . kg(-1) . min(-1), P = 0.001). Prandial-like peripheral hyperinsulinemia completely suppressed EGP during both protocols, whereas whole-body rate of glucose disappearance (R(d)) was approximately 33% lower during amino acid infusion (R(d) (330-360 min) 50 +/- 4 vs. 75 +/- 6 mumol . kg(-1) . min(-1), P = 0.002) indicating insulin resistance. In skeletal muscle biopsies taken before and after prandial-like peripheral hyperinsulinemia, plasma amino acid elevation markedly increased the ability of insulin to activate S6 kinase 1 compared with saline infusion ( approximately 3.7- vs. approximately 1.9-fold over baseline). Furthermore, amino acid infusion increased the inhibitory insulin receptor substrate-1 phosphorylation at Ser312 and Ser636/639 and decreased insulin-induced phosphoinositide 3-kinase activity. However, plasma amino acid elevation failed to reduce insulin-induced Akt/protein kinase B and glycogen synthase kinase 3alpha phosphorylation. In conclusion, amino acids impair 1) insulin-mediated suppression of glucose production and 2) insulin-stimulated glucose disposal in skeletal muscle. Our results suggest that overactivation of the mammalian target of rapamycin/S6 kinase 1 pathway and inhibitory serine phosphorylation of insulin receptor substrate-1 underlie the impairment of insulin action in amino acid-infused humans.

Adult↗

PubMed1979

Parenteral nutrition in severely burned children.

In adults supplemental parenteral nutrition (PN) is advisable in burns over 40% especially when weight loss exceeds 10% of body weight. In children with smaller reserves and higher requirement of proteins and energy no rigid scheme for parenteral supplementation is used at our unit. In a young infant it may be added already at a 20-30% deep burn, especially with connected gastrointestinal tract problems, infection etc. Metabolic and protein requirements are estimated 50-100% in addition to their normal needs. Hypertonic glucose (gradually increased from 20-40%), covered with insulin in the early phase, is used as source of carbohydrates. L-amino acid mixture containing the "pediatric essential amino acids" histidine and cysteine is given as a nitrogen source. 20% Intralipid is given in a gradually increased amount of 2-4 g/kg per day to provide calories and essential fatty acids. Among electrolytes K, Ca, P and Mg must be added. Increased amounts of vitamin C and folate are needed by burned children. Vitamin E is also required during prolonged lipid administration. Trace elements (Zn. Fe, etc.) are supplied orally or i.v. with special solutions or fresh plasma infusions. Our experience with parenteral nutrition in severely burned children will be presented. There were no severe metabolic side-effects but sepsis represented the major problem. The concomitant heat preservation by warming the room and use of infra-red heaters is emphasized.

Body Weight↗

PubMed1994

Racemization of tyrosine in the insoluble protein fraction of brunescent aging human lenses.

With increase in age, proteins of the eye lens undergo covalent modifications associated with interprotein cross-linking, loss of protein solubility, generation of protein-associated pigments, and racemization of some optically active residues. Precipitated protein aggregates localized in the nucleus of brunescent lenses are modified to such an extent that they become resistant to the commonly used methods of extraction by reducing agents or detergents. Thus, little information is available on the types of protein modifications that occur in the nuclear region of the lens. Here we report the simultaneous solubilization and digestion of the entire nuclear pellet of brunescent human cataract lenses into constituent amino acids and their derivatives through protease action at neutral pH. Fractionation of the resulting hydrolyzate by reverse phase chromatography, followed by spectroscopic and biochemical analysis of one of the purified fractions, showed the presence of racemic tyrosine in the amino acid mixture. Racemization of L-amino acid residues in protein chains is associated with the aging process. This is the first report of racemization of tyrosine in any system studied so far.

Aging↗

PubMed1974

Amino acid imbalance in cystinuria.

After oral ingestion of a free amino acid mixture by three cystinuric patients, plasma increments of lysine and arginine were lower and those of many other amino acids were significantly higher than those found in control subjects. Similar results were obtained in control subjects after amino acid imbalance had been artificially induced by the omission of cystine, lysine, and arginine from the amino acid mixture. Especially high increments of alanine and proline provided the best evidence of amino acid imbalance caused by a temporary lysine and, to a lesser extent, arginine and cystine deficit. No such amino acid imbalance was found to occur in the cystinuric patients after ingestion of whole protein, indicating that absorption of oligopeptides produced by protein digestion provided a balanced physiological serum amino acid increment. This is considered to explain the lack of any unequivocal nutritional deficit in cystinuric patients despite poor absorption of the essential free amino acid, lysine.

Adult↗

PubMed2003

Amino acid composition of soybean protein increased postprandial carbohydrate oxidation in diabetic mice.

The effects of an amino acid mixture simulating dietary soybean protein on the postprandial energy metabolism was investigated using type II diabetic mice. KK-A(y) strain mice were fed restrictive isoenergetic and isonitrogenous diets (35% of energy as protein and 5% as fat) based on either casein, soybean protein isolate hydrolysate (SPI-H), SPI-HET (ethanol unsoluble fraction of SPI-H), SPI-AA and casein-AA (amino acid mixtures simulating SPI-H and casein). To measure dietary carbohydrate oxidation, the animals were fed a diet containing (13)C-glucose. Postprandial respiratory quotient and expired (13)CO(2) were higher in the SPI-AA than in the casein-AA group, as the differences were similarly observed in mice fed SPI-H and casein diet. No significant differences were observed in the postprandial respiratory quotient and expired (13)CO(2) between the SPI-H and SPI-HET group. In conclusion, this study on food-restricted mice indicates that the amino acid mixtures simulating SPI-H or casein could affect postprandial energy metabolism in diabetic mice, as observed in those fed SPI-H or casein in the form of peptide or protein.

Amino Acids↗

PubMed1996

Learned olfactory discrimination of amino acids and their binary mixtures in bullhead catfish (Ameiurus nebulosus).

The question of whether bullhead catfish can discriminate binary mixtures of amino acids from the individual components of the mixture was investigated. Two groups of catfish were conditioned to different binary mixtures of L-norvaline (NVAL) and L-leucine (LEU). The concentrations of the amino acids in the conditioned mixtures were adjusted so that in different mixtures either NVAL or LEU was the more stimulatory component. Bullhead catfish were unable to discriminate the more stimulatory components, but were able to discriminate the less stimulatory components and other amino acids from the conditioned mixtures. The third group of bullhead catfish was conditioned to L-proline (PRO) and the responses to different mixtures of PRO and NVAL were subsequently evaluated. Behavioral and electrophysiological (EOG) experiments indicated that the difference in relative stimulatory effectiveness levels between NVAL and PRO is > 30,000 times. For subsequent tests, the concentrations of PRO and NVAL were adjusted to form binary mixtures in which PRO and NVAL, respectively, were the more stimulatory components. Bullhead catfish conditioned to PRO discriminated the mixture if NVAL was the more stimulatory component, but did not discriminate PRO from the mixture if PRO was the more stimulatory component. These results suggest that binary mixtures of amino acids are initially perceived as the more stimulatory components of the mixture.

Amino Acids↗