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)

Several in vivo studies have indirectly suggested a relationship between blood glutamine and ketonemia. The present study was designed to characterize the role glutamine plays in regulating lipolysis and ketogenesis during fasting in vivo. Twelve dogs had catheters implanted in the hepatic and portal veins (V) and in the femoral artery (A) 17-21 days before study. The animals were fasted for 4 days. After a 120-min rest and 40-min basal periods, 6 dogs received an infusion of L-glutamine at 6 mumol X kg-1 X min-1 and 6 received saline and acted as controls. Hepatic and splanchnic balances (mumol X kg-1 X min-1) were estimated by A-V differences multiplied by blood flow determined by indocyanine green. Fasting was associated with a compensated (no change in pH) mild metabolic acidosis but no change in plasma insulin and glucagon or blood glutamine. L-Glutamine infusion increased blood glutamine by 20% but decreased arterial free fatty acids (FFA, from 1,054 +/- 47 to 850 +/- 43 mumol/l, P less than 0.01), beta-hydroxybutyrate (beta-OHB, from 136 +/- 15 to 66 +/- 8 mumol/l, P less than 0.01), acetoacetate (AcAc, from 168 +/- 26 to 86 +/- 21 mumol/l, P less than 0.01), and glycerol (from 90 +/- 4 to 65 +/- 5 mumol/l, P less than 0.01). It also decreased hepatic uptake of glycerol (from 2.5 +/- 0.5 to 0.8 +/- 0.3 mumol X kg-1 X min-1, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine blocks lipolysis and ketogenesis of fasting. 351 12

In F344 rats bearing transplantable 3-methylcholanthrene (CAS: 56-49-5)-induced sarcomas, plasma concentrations of immunoreactive insulin were decreased following the development of mild or severe anorexia. Plasma levels of immunoreactive glucagon and lactate were elevated in severely anorectic tumor-bearing (TB) rats, while plasma glucose concentrations remained normal. Both groups of TB rats exhibited decreased plasma levels of serine, glutamine, citrulline, and tryptophan and increased concentrations of alanine. Plasma levels of proline and phenylalanine were also elevated in the severely anorectic TB rats. In a second experiment, 7 daily treatments with insulin corrected the anorexia for 6 days and increased body weights of TB rats. Plasma concentrations of lactate and immunoreactive glucagon were decreased, and the abnormal plasma concentrations of glutamine, proline, analine, and phenylalanine were altered toward normal following the insulin treatments. Therefore, these data are consistent with insulin treatments benefiting the TB host by increasing feeding, increasing body weight, reducing tumor glycolysis and metabolism, reducing gluconeogenesis, and reducing host catabolism, while not stimulating tumor growth. Thus insulin therapy may have potential benefits in cancer treatment by shifting glucose metabolism toward the host and away from the tumor.
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PMID:Reversal of tumor-induced biochemical abnormalities by insulin treatment in rats. 352 58

A dramatic increase in the plasma glucagon/insulin ratio can be induced by treating fasted rats with antilipolytic drugs (e.g., with 3,5-dimethylpyrazole, 12 mg/kg body wt). These hormone changes are the physiologically appropriate response to a rapid decrease in free fatty acids and glucose plasma levels. Under this experimental condition, many vacuolated lysosomes can be observed at the electron microscopic level as early as 30 min and autophagic vacuoles are detectable in the liver cells 1 hr after the administration of the drug. By 1 hr and 45 min, vacuoles often contain recognizable peroxisomes. At the biochemical level, liver proteolysis in vitro is increased significantly. Very interestingly, changes in peroxisomal (but not mitochondrial or reticulum or cytosolic) enzyme activities are detected that are preventable by the administration of glutamine (i.e., of an inhibitor of proteolysis in vivo) but not by an isocaloric amount of glycine or alanine. It is concluded that the administration of antilipolytic agents to fasted animals may provide a convenient (i.e., an inexpensive, highly reproducible and timable) physiologic model to study hormone-induced autophagy in liver cells.
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PMID:Increased degradation in rat liver induced by antilipolytic agents: a model for studying autophagy and protein degradation in liver? 354 50

The liver is innervated by sympathetic and parasympathetic nerves. The effects and mechanisms of actions of hepatic nerves were studied in the isolated rat, guinea pig and Tupaia liver perfused in a non-recirculating manner either via the portal vein or via both the hepatic artery and the portal vein. The arterial plexus was stimulated at the common hepatic artery, the portal plexus at the mesenteric vein or both plexus jointly at the artery and the portal vein in the liver hilus (1-20 Hz, 2 ms, 20 V, 0.5-5 min). Upon nerve stimulation sympathetic effects clearly predominated; parasympathetic actions could only be demonstrated in the presence of alpha- and beta-antagonists. Sympathetic stimulation increased glucose output, shifted lactate uptake to output, decreased ketone body, urea and glutamine formation as well as ammonia uptake, lowered oxygen uptake, reduced perfusion flow combined with an intrahepatic redistribution and perfusate mobilization, and caused an overflow of noradrenaline into the hepatic vein. All effects were mediated predominantly via alpha-receptors; they were dependent on extracellular calcium. Some effects were modulated by hormones: the glucagon-mediated increase of glucose output was further enhanced but that of lactate uptake was decreased by nerve stimulation; in the presence of insulin glucose output was increased only slightly. Parasympathetic stimulation had no effect on basal metabolism or hemodynamics. Yet, it antagonized the glucagon-stimulated glucose release and enhanced the slight, insulin-dependent increase of glucose utilization. The sympathetic nerves may act directly at the parenchymal cells or indirectly via an overflow of neurotransmitter from the vasculature or via hemodynamic changes. Experiments with the vessel relaxant sodium nitroprusside and with retrograde perfusion indicate that neither hemodynamic alterations nor noradrenaline overflow from the vasculature play a major role in the sympathetic alterations in glucose and lactate metabolism; rather the nerves appear to act directly within the parenchyma. Comparative studies with rat, guinea pig and tupaia livers corroborate the view that the sympathetic nerves act in the rat via contacts to only a few periportal hepatocytes with signal propagation through gap junctions, while they act in the guinea pig and tupaia via contacts to almost all parenchymal cells. Sympathetic nerve stimulation caused an increase in the activity of glycogen phosphorylase and a decrease of glycogen synthase; it left the activity of pyruvate kinase and the levels of fructose 2.6-bisphosphate and cyclic AMP unaltered.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Regulation of liver metabolism and hemodynamics by the hepatic nerves]. 359 Sep 3

Adenosine and inosine produced a dose-dependent stimulation of ureagenesis in isolated rat hepatocytes. Hypoxanthine, xanthine and uric acid were without effect. Half-maximally effective concentrations were 0.08 microM for adenosine and 5 microM for inosine. Activation of ureagenesis by both nucleosides had the following characteristics: (a) it was observed with either glutamine or (NH4)2CO3, provided that glucose was present; (b) it was not detected when glucose was replaced by lactate plus oleate; (c) it was mutually antagonized by glucagon, but not by adrenaline; and (d) it was dependent on Ca2+. We suggest that the action of adenosine and inosine on ureagenesis might be of physiological significance.
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PMID:Effect of adenosine and inosine on ureagenesis in hepatocytes. 366 62

In the isolated rat liver perfused as usual via the portal vein, joint electrical stimulation of the nerve fibers around the artery and the portal vein in the liver hilus increased glucose output, shifted lactate uptake to output, decreased urea and glutamine formation as well as ammonia uptake, reduced ketone body production, lowered oxygen uptake and reduced perfusion flow simultaneously changing the intrahepatic flow distribution; it was accompanied by an overflow of noradrenaline into the hepatic vein. All effects were mediated predominantly via alpha-receptors; they were dependent on extracellular calcium. In livers perfused both via the artery and the portal vein, separate stimulation of the plexus at the common hepatic artery or at the portal vein caused similar effects on glucose and lactate balance and on perfusion flow. Arterial stimulation caused the higher metabolic responses and alterations not only in arterial but also 'transhepaticly' in portal flow, and conversely, portal flow elicited the smaller metabolic responses and alterations in both portal and 'transhepaticly' arterial flow. If sympathetic nerve actions were blocked using alpha- and beta-antagonists, the resulting parasympathetic stimulation increased glucose uptake in the presence of insulin and antagonized the glucagon stimulated glucose release, both alone and more strongly in the presence of insulin. The sympathetic nerves may act directly at the parenchymal cells or indirectly via an overflow of neurotransmitter from the vasculature into the sinusoids or via hemodynamic changes. Experiments with the smooth muscle relaxant sodium nitroprusside and with retrograde flow indicate that neither hemodynamic changes nor noradrenaline overflow from the vasculature can play a major role in the mechanism of action of sympathetic liver nerves on glucose and lactate metabolism. Comparative studies with perfused livers of rats, guinea pigs and tupaias are in line with the view that in the rat the sympathetic nerves act via contacts with only a few periportal hepatocytes, from where the signal is propagated through gap junctions, while in guinea pig and tupaia the nerves act via contacts with almost all parenchymal cells. Sympathetic nerve stimulation of the perfused rat liver caused an increase in the activity of glycogen phosphorylase and a decrease of glycogen synthase, but left the activity of pyruvate kinase unaltered; fructose 2,6-bisphosphate and cAMP were only slightly enhanced.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of liver metabolism by the hepatic nerves. 367 10

It has been suggested that the monokine tumor necrosis factor (TNF) (cachectin) is responsible for metabolic abnormalities frequently accompanying malignant neoplasms. The acute metabolic effects of TNF in patients with cancer were studied. Subcutaneous administration of recombinant human TNF led to a rise in the C-reactive protein level (4.4 +/- 1.2 mg/dL vs 11.6 +/- 1.8 mg/dL) and a reduction in the serum zinc level (12.9 +/- 0.8 mumol/L vs 7.3 +/- 0.8 mumol/L [79 +/- 5 mg/dL vs 48 +/- 5 mg/dL]) (values are the mean +/- SEM). Forearm efflux of total amino acids more than doubled after intravenous TNF injection, principally because of increases in release of the gluconeogenic amino acids alanine and glutamine. Concomitantly, the arterial levels of alanine, glutamine, and total amino acids fell, indicating that TNF also stimulated the uptake of amino acids by other tissues. The observed amino acid pattern cannot be explained solely on the basis of measured changes in cortisol, glucagon, or insulin levels. These findings are discussed in relation to known alterations of amino acid metabolism in cancer-associated cachexia.
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PMID:The acute metabolic effects of tumor necrosis factor administration in humans. 368 16

The nervous control of hepatic urea and glutamine release and of ammonia uptake was studied in the rat liver perfused in situ. Electrical stimulation of the nerve bundles around the hepatic artery and the portal vein resulted in a reduction of urea release, of glutamine output and of ammonia uptake. At the same time, as observed before [Hartmann et al. (1982) Eur. J. Biochem. 123, 521-526], nerve stimulation led to a decrease of portal flow as well as to an increase of glucose release and a shift of lactate uptake to output. Noradrenaline infusion mimicked the nerve-dependent metabolic and hemodynamic changes in a first approximation only at the highly unphysiological concentration of 0.1 microM. It was without effect at 0.01 microM, which might be reached in the sinusoids as a result of overflow from the vasculature. In the presence of sodium nitroprusside nerve stimulation no longer reduced urea output, glutamine release and ammonia uptake or portal flow, yet it still increased glucose and lactate release. Phentolamine clearly reduced the alterations after nervous stimulation of urea output, ammonia uptake and portal flow, while propranolol was essentially not effective. The nerve-stimulation-dependent reduction of glutamine release was almost abolished in the presence of phentolamine and lowered to 50% by propranolol. Glucagon stimulated urea output but had no influence on glutamine release, ammonia uptake and portal flow. Nerve stimulation antagonized the glucagon-stimulated urea release. The present results suggest that in the perfused liver alpha-sympathetic hepatic nerves regulate urea release, glutamine output and ammonia uptake predominantly by an indirect mechanism via hemodynamic alterations, but glucose release by a direct mechanism also in the absence of circulatory changes.
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PMID:Control of urea production, glutamine release and ammonia uptake in the perfused rat liver by the sympathetic innervation. 373 64

We carried out metabolic investigations of 26 patients with severe forms of acute pancreatitis which were evaluated by an organ score. We formed six groups from this data: survivors and deceased in the first week, the second week, and after a further two weeks of illness. The amino acid patterns in plasma and muscles deviated considerably from normal at all times in both the surviving and the deceased patients. In particular, changes in the concentrations of branched-chain amino acids and glutamine in the muscle tissue have a prognostic value. In the range two to four (normal range: above 20), the factor glutamine/VAL+LEU+ILE characterizes a prefinal condition in non-survivors. This factor increased in patients recovering from the illness from 6 to values over 20. Non-survivors (NS) had higher plasma levels of glucose and glucagon compared to surviving patients. Plasma glucagon concentrations in NS reached levels up to 4,000 pg/mL at admission, which declined gradually to normal range during the course of the illness.
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PMID:Metabolic changes of patients with acute necrotizing pancreatitis. 375 30

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


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