Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Glucagon stimulated gluconeogenesis from glutamine in isolated liver cells to a far greater extent than that from any other amino-acid precursor. 2. Low concentrations of ammonium chloride (less than 1 mM) stimulated glucose production from glutamine. Glucagon further stimulated this glucose production, even in the presence of saturating concentrations of ammonium chloride. 3. In agreement with previous reports, glutamine hydrolysis by isolated mitochondria was found to be stimulated by ammonium chloride. It was found that ammonium chloride activated mitochondrial glutamine hydrolysis at the same concentrations at whict it stimulated glucose production from glutamine in liver cells. The effective activation of glutamine hydrolysis by ammonimum chloride in intact mitochondria was partially inhibited by rotenone and was abolished by uncoupling agents. 4. The addition of glucagon to hepatocytes metabolising glutamine led to a decrease in the intracellular concentration of glutamine and an increase in the intracellular concentration of glutamate. 5. It is likely that glucagon stimulates gluconeogenesis from glutamine by mechanisms which are additional to those that may operate in the stimulation of gluconeogenesis from other amino-acid precursors. It is suggested that both ammonium chloride and glucagon exert their effects on glutamine metabolism by increasing the effective activity of mitochondrial glutaminase (EC 3.5.1.2.).
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PMID:The effect of ammonium chloride and glucagon on the metabolism of glutamine in isolated liver cells from starved rats. 70 83

The metabolism of skeletal muscle glutamine was studied in rats made septic by cecal ligation and puncture technique. Blood glucose was not significantly different in septic rats, but lactate, pyruvate, glutamine, and alanine were markedly increased. Conversely, blood ketone body concentrations were markedly decreased in septic rats. Both plasma insulin and glucagon were markedly elevated in septic rats. Sepsis increased the rates of glutamine production in muscle, but without marked effects on skin and adipose tissue preparations, with muscle production accounting for over 87% of total glutamine produced by the hindlimb. Sepsis produced decreases in the concentrations of skeletal muscle glutamine, glutamate, 2-oxoglutarate, and adenosine monophosphate (AMP). The concentrations of ammonia, pyruvate, and inosine monophosphate (IMP) were increased. Hindlimb blood flow showed no marked change in response to sepsis, but was accompanied by an enhanced net release of glutamine and alanine. The maximal activity of glutamine synthetase was increased only in quadriceps muscles of septic rats, whereas that of glutaminase was decreased in all muscles studied. Tyrosine release from incubated muscle preparation was markedly increased in septic rats; however, its rate of incorporation was markedly decreased. It is concluded that there is an enhanced rate of production of glutamine from skeletal muscle of septic rats. This may be due to changes in efflux and/or increased intracellular formation of glutamine; these suggestions are discussed.
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PMID:Glutamine metabolism in skeletal muscle of septic rats. 167 Nov 65

1. Glutaminase activity was measured in primary cultures of hepatocytes. 2. Enzyme activity decreased markedly after 24-40 h in culture, and this loss of activity was accompanied by loss of enzyme protein. 3. The loss of activity was delayed by high concentrations of glutamine, and was abolished by the continuous presence of NH4Cl in the culture medium. 4. In cells from rats fed on high-carbohydrate protein-free diet, glutaminase activity was increased by glucagon, but not by dexamethasone. This induction was observed only in the continuous presence of NH3 or high concentrations of glutamine. 5. It is concluded that NH3 and glutamine are essential for the stabilization and induction of glutaminase activity in hepatocytes. The inactivation of glutaminase in hepatocytes and in vivo under certain conditions may be due to lack of NH3 in the extracellular medium.
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PMID:Glucagon and ammonia influence the long-term regulation of phosphate-dependent glutaminase activity in primary cultures of rat hepatocytes. 200 Dec 24

The intestinal metabolism of glucose and glutamine was studied in rats made septic by cecal ligation and puncture technique. Sepsis resulted in negative nitrogen balance and produced increases in the concentrations of blood pyruvate, lactate, alanine, and glutamine, and decreases in those of 3-hydroxybutyrate and acetoacetate. Both plasma insulin and glucagon concentrations were increased by 2.2- and 3.2-fold in septic rats, respectively. Portal-drained visceral blood flow increased in septic rats, and was accompanied by a decrease in the rates of utilization of glutamine and production of lactate, glutamate, and ammonia compared with those rates in sham-operated animals. Enterocytes isolated from septic rats showed decreased rates of glucose and glutamine utilization compared with cells isolated from corresponding controls. The maximal activities of hexokinase, 6-phosphofructokinase, pyruvate kinase, and glutaminase were decreased in intestinal mucosal scrapings of septic rats. It is concluded that a moderate form of sepsis decreases the rates of glucose and glutamine utilization (both in vivo and in vitro) by the epithelial cells of the small intestine. This may be caused by changes in the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells as a metabolic adaptation to spare glucose and glutamine for use by other tissues.
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PMID:Glucose and glutamine metabolism in the small intestine of septic rats. 236 28

The effects of chronic uraemia on glucose production and nitrogen release (urea plus ammonia formation) from alanine, glutamine or serine in isolated rat hepatocytes were studied. Uraemia increased the rate of formation of urea plus ammonia from all three amino acids by 38-93% when they were present at a final concentration of 10 mmol/l. At lower concentrations (2 mmol/l) the rate of nitrogen release was not significantly increased. Hepatocytes from normal rats whose food intake had been restricted to the level of that of uraemic rats did not show the increased rates of nitrogen release. The increased rates of nitrogen release with hepatocytes from uraemic rats were not accompanied by increased rates of glucose synthesis. Instead, accumulation of metabolic intermediates occurred: lactate and pyruvate (alanine or serine as substrates) and glutamate (glutamine as substrate). Livers of uraemic rats had increased activities of glutaminase (30%) and serine dehydratase (100%). Hepatocytes from normal rats treated with phlorhizin to increase the plasma glucagon/insulin ratio behaved in a similar manner to hepatocytes from uraemic rats. They had increased serine dehydratase activity, and increased rates of utilization of serine or glutamine. The possible implications of these findings for human uraemia are discussed.
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PMID:Effects of chronic uraemia on the formation of glucose and urea plus ammonia from L-alanine, L-glutamine and L-serine in isolated rat hepatocytes. 308 21

Glutamine stimulated glycogen synthesis and lactate production in hepatocytes from overnight-fasted normal and diabetic rats. The effect, which was half-maximal with about 3 mM-glutamine, depended on glucose concentration and was maximal below 10 mM-glucose. beta-2-Aminobicyclo[2.2.1.]heptane-2-carboxylic acid, an analogue of leucine, stimulated glutaminase flux, but inhibited the stimulation of glycogen synthesis by glutamine. Various purine analogues and inhibitors of purine synthesis were found to inhibit glycogen synthesis from glucose, but they did not abolish the stimulatory effect of glutamine on glycogen synthesis. The correlation between the rate of glycogen synthesis and synthase activity suggested that the stimulation of glycogen synthesis by glutamine depended solely on the activation of glycogen synthase. This activation of synthase was not due to a change in total synthase, nor was it caused by a faster inactivation of glycogen phosphorylase, as was the case after glucose. It could, however, result from a stimulation of synthase phosphatase, since, after the addition of 1 nM-glucagon or 10 nM-vasopressin, glutamine did not interfere with the inactivation of synthase, but did promote its subsequent re-activation. Glutamine was also found to inhibit ketone-body production and to stimulate lipogenesis.
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PMID:Stimulation of glycogen synthesis and lipogenesis by glutamine in isolated rat hepatocytes. 312 12

The metabolic effects of beta-(+/-)-2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid (BCH), a nonmetabolizable analog of leucine and known activator of glutamate dehydrogenase, were studied in hepatocytes isolated from fed and fasted rats. With glutamine as substrate, BCH stimulated in a concentration-dependent manner urea synthesis in both physiological states and glucose formation in hepatocytes from fasted rats. Despite the much higher rates of ureagenesis in the fasted animals, the degree of stimulation by BCH, over 2-fold, was similar. The effect of the drug was specific for glutamine since the rates of urea synthesis from NH4Cl, alanine, and asparagine were essentially unaltered. The stimulation of glutamine catabolism by BCH led to a decrease in the content of intracellular glutamine. The redox states of the mitochondrial and cytosolic nicotinamide adenine dinucleotides remained unaltered. In hepatocytes isolated from fasted rats and incubated with 5 mM glutamine the BCH-induced increases in urea, ammonia, and the amino acids, glutamate, aspartate, and alanine, accounted fully for the 2.4-fold rise in glutamine utilization. The stimulatory effects of BCH and glucagon on the formation of glucose, urea, and 14CO2 from [U-14C]glutamine were additive. Aminooxyacetate, and inhibitor of transaminases, neither blocked glutamine catabolism (as measured by the sum of urea, ammonia, and glutamate) nor prevented its activation by BCH. It is suggested that, in isolated hepatocytes, BCH-induced stimulation of glucose and urea formation from glutamine results from activation of glutaminase by a mechanism which is distinct from that of glucagon.
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PMID:Glutamine metabolism in rat hepatocytes. Stimulation by a nonmetabolizable analog of leucine. 377 24

1. Glutaminase and glutamine synthetase are simultaneously active in the intact liver, resulting in an energy consuming cycling of glutamine at a rate up to 0.2 mumol per g per min. 2. An increase in portal glutamine concentration was followed by an increased flux through glutaminase, but flux through glutamine synthetase remained unchanged. Glutaminase flux was also increased by ammonium ions or glucagon; these effects were additive. 3. Glutamine synthetase flux was increased by ammonium ions, but this activation was partly overcome by increasing portal glutamine concentrations. Glutamine synthetase flux was slightly increased by glucagon at portal glutamine concentrations of about 0.2-0.3 mM, but was strongly inhibited above 0.6 mMs. 4. During experimental metabolic acidosis there was an increased net release of glutamine by the liver, being due to opposing changes of flux through glutaminase and glutamine synthetase. Conversely, an increased glutamine uptake by the liver during metabolic alkalosis was observed due to an inhibition of glutamine synthetase and an activation of glutaminase. However, the two enzyme activities respond differently depending on whether glucagon or ammonium ions are present.
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PMID:Regulation of flux through glutaminase and glutamine synthetase in isolated perfused rat liver. 613 95

Glucagon injected into rats caused an increase in liver N-acetylglutamate content, and coincidentally the glutamate content decreased. The liver glutamine content decreased only after 10 min, consistent with an activation of glutaminase after a lag. These observations indicate that the increased N-acetylglutamate content was not due to an increase in glutamate content caused by an activation of glutaminase (EC 3.5.1.2).
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PMID:Effects of glucagon in vivo on the N-acetylglutamate, glutamate and glutamine contents of rat liver. 614 51

Addition of phenylephrine to isolated perfused rat liver is followed by an increased 14CO2 production from [1-14C]glutamate, [1-14C]glutamine, [U-14C]proline and [3-14C]pyruvate, but by a decreased 14CO2 production from [1-14C]pyruvate. Simultaneously, there is a considerable decrease in tissue content of 2-oxoglutarate, glutamate and citrate. Stimulation of 14CO2 production from [1-14C]glutamate is also observed in the presence of amino-oxyacetate, suggesting a stimulation of glutamate dehydrogenase and 2-oxoglutarate dehydrogenase fluxes by phenylephrine. Inhibition of pyruvate dehydrogenase flux by phenylephrine is due to an increased 2-oxoglutarate dehydroxygenase flux. Phenylephrine stimulates glutaminase flux and inhibits glutamine synthetase flux to a similar extent, resulting in an increased hepatic glutamine uptake. Whereas the effects of NH4+ ions and phenylephrine on glutaminase flux were additive, activation of glutaminase by glucagon was considerably diminished in the presence of phenylephrine. The reported effects are largely overcome by prazosin, indicating the involvement of alpha-adrenergic receptors in the action of phenylephrine. It is concluded that stimulation of gluconeogenesis from various amino acids by phenylephrine is due to an increased flux through glutamate dehydrogenase and the citric acid cycle.
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PMID:Effect of phenylephrine on glutamate and glutamine metabolism in isolated perfused rat liver. 614 74


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