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)

The mechanisms whereby tryptophan administration leads to hypoglycaemia in some groups of rats but not others have been investigated. Animals insensitive to tryptophan are rendered responsive by adrenalectomy. This effect is reversed by steroid replacement. Turnover studies with [2-3H]glucose show that hypoglycaemia in sensitive animals is associated with a decrease in glucose synthesis. Tryptophan administration causes a marked and sustained increase in plasma glucagon concentrations in all animals. The locus of the inhibition of gluconeogenesis in tryptophan-sensitive animals is the reaction catalysed by phosphoenolpyruvate carboxykinase. The sensitivities to tryptophan of gluconeogenesis in isolated hepatocytes from normal and adrenalectomized animals were similar. Cells from chronically streptozotocin-diabetic animals required higher concentrations of the amino acid for the same effect. These results are discussed in relation to previous discrepancies in the literature, and a unifying hypothesis for tryptophan-induced hypoglycaemia is proposed.
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PMID:Factors affecting tryptophan-induced hypoglycaemia in rats. 718 38

Pretreatment of rats with increasing, but non-lethal, doses of endotoxin was associated with a parallel increase in sensitivity to induction of hypoglycaemia by tryptophan. Acutely streptozotocin-diabetic animals became hypoglycaemic with endotoxin alone, and this was increased further by tryptophan. Variations in tryptophan sensitivity between rat populations cannot be explained by previous history of exposure to endotoxin. Endotoxin abolished the increase in tryptophan dioxygenase activity caused by triamcinolone, but not that caused by tryptophan. Triamcinolone was effective, however, when given together with tryptophan to endotoxin-treated rats. The activity of tryptophan dioxygenase in vivo and in liver cells in vitro is unchanged by exposure to endotoxin at 1 mg/kg body wt. Turnover studies indicated that hypoglycaemia resulted from inhibition of gluconeogenesis. There was no evidence to support a role for insulin in this process and results were consistent with an endotoxin-mediated hepatic insensitivity to glucagon. They also suggested that quinolinate, rather than 5-hydroxytryptamine, may be the intracellular agent responsible for inhibition of gluconeogenesis.
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PMID:Endotoxin and tryptophan-induced hypoglycaemia in rats. 718 39

The response of the plasma substrate and hormone profile of survivor and nonsurvivor septic trauma patients to varying rates of amino acid infusion (IVAA) were contrasted. When IVAA=0 levels of most plasma amino acids (except aspartate, tryptophan, cysteine, and proline) were lower in nonsurvivors. At IVAA=1 to 100, however, 11 of 20 plasma amino acids were significantly (p less than or equal to 0.05) higher in nonsurvivors: only glutamate was significantly lower (p less than or equal to 0.001) and valine, isoleucine, and arginine on average lower. At IVAA less than or equal to 101 to 200, only alanine, methionine, tyrosine, and phenylalanine were significantly (p less than or equal to 0.005) higher in nonsurvivors; isoleucine was significantly (p less than or equal to 0.02) lower. The sharp increase in methionine and decrease in tryptophan in nonsurvivors with IVAA was particularly marked. Polynomial regression analysis showed that urea increased significantly with IVAA in both patient groups, while free fatty acids and cortisol decreased only in nonsurvivors. Insulin increased with IVAA only in survivors, glucagon only in nonsurvivors. Triglycerides, glycerol, acetoacetate, beta OH butyrate, and glucose appeared to show no significant response to IVAA in either patient group. The data are consistent with increased peripheral protein catabolism and branched-chain amino acid oxidation in association with decreased tissue uptake of conventional energetic fuels. These results may be interpreted to be consistent with an impairment of mitochondrial translocase systems.
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PMID:Multiple systems organ failure: III Contrasts in plasma amino acid profiles in septic trauma patients who subsequently survive and do not survive-effects of intravenous amino acids. 721 92

Acute hepatic ischaemia was induced in pigs by means of a portacaval shunt with hepatic artery ligation after 24 hours. Despite significant elevation in blood ammonia, fatty acids, aspartate aminotransferase, cerebrospinal fluid glutamine and ammonia, and brain tissue glutamine, ammonia and tryptophan, the experimental animals remained awake and alert and indistinguishable from sham-operated controls. The molar ratio of branched-chain to aromatic amino acids fell sharply in the arterial blood, but showed a terminal attempt at compensation in muscle venous samples. Portal and muscle venous insulin levels were elevated, and glucagon values rose in all circulation segments in the experimental group. The failure to induce coma in these pigs, despite the presence of many of the classical biochemical features, suggests that the syndrome of encephalopathy comprises several stages, and that the pig may be an important model in which to define these.
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PMID:Acute hepatic ischaemia in the pig- the changes in plasma hormones, amino acids and brain biochemistry. 725 Aug 93

Developmental increase of tryptophan oxygenase (L-tryptophan: oxygen 2, 3-oxidoreductase (decyclizing), EC 1.13.11.11) was studied using hepatocytes of neonatal rats in primary culture. Hepatocytes from rats of 2-30-days-old were isolated and cultured for 2 days. In cultured hepatocytes of 2-day-old rats, tryptophan (2.5 mM), dexamethasone (1 x 10(-5) M) and glucagon (1 x 10(-7) M) did not cause the appearance of tryptophan oxygenase. But the enzyme activity became detectable, when hepatocytes from 5-day-old rats were incubated with tryptophan, the oxygenase could be induced precociously by dexamethasone, but by glucagon. The effect of glucagon was first seen 2 weeks after birth. However, in hepatocytes of 9-day-old rats glucagon stimulated formation of cyclic AMP and protein kinase activity (EC 2.7.1.37) and also induced tyrosine aminotransferase (EC 2.6.1.5). When hepatocytes of 9-day-old rats were cultured for 4 days, their tryptophan oxygenase became inducible by glucagon. Insulin almost completely inhibited precocious appearance of the enzyme activity evoked by tryptophan plus dexamethasone in hepatocytes of 9-day-old rats. These studies suggest that the appearance of tryptophan oxygenase in rat liver during development is due to first the onset of gene coding for tryptophan oxygenase and then stimulation by the sequential actions of glucocorticoid and glucagon.
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PMID:Hormonal control of the development of tryptophan oxygenase in primary cultures of young rat hepatocytes. 730 79

The synthesis of the heterobifunctional cross-linking reagent 2-nitro-4-azidophenylsulfenyl chloride (NAPSCl) is described. This reagent can be used to specifically attach a photoactivatable nitrophenyl azide to tryptophan-containing polypeptides and proteins lacking sulfhydryl groups. The sulfenyl chloride group of NAPSCl reacts with the indole ring of tryptophan following second-order reaction kinetics in 50-100% acetic acid. The labeled product can be effectively photolyzed at wavelengths above 300 nm. The reaction of glucagon, a peptide hormone containing a single tryptophan residue at position 25 and no cysteine, with NAPSCl gave one major product, the photosensitive derivative glucagon-NAPS. The structure and properties of the purified derivative were established by amino acid analysis, absorption spectroscopy, and photolysis. Only the tryptophan residue of this derivative was modified. The photosensitive glucagon was shown to activate the adenylate cyclase of hepatocyte plasma membranes to the same extent as the native hormone at equimolar concentrations. Glucagon-NAPS could be radiolabeled by the lactoperoxidase-catalyzed iodination of the peptide. A glucagon-specific antibody bound both radiolabeled glucagon and glucagon-NAPS peptides. The covalent labeling of protein molecules with radiolabeled glucagon-NAPS peptide upon photolysis was demonstrated. Glucagon-NAPS can be used as an effective photoaffinity probe for labeling the glucagon receptor site in plasma membranes of target cells.
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PMID:Synthesis and characterization of a heterobifunctional photoaffinity reagent for modification of tryptophan residues and its application to the preparation of a photoreactive glucagon derivative. 742 13

Previous experiments suggest that experimental cancer-induced anorexia is associated with hyperammonemia and that daily injections of insulin may attenuate the anorexia for several days. In the present study, we determined whether similar daily insulin treatments would correct anorexia induced by the infusion of ammonium salts and compared this feeding response with that of insulin-treated tumor-bearing (TB) rats. Daily treatment of control and anorectic TB rats with systemically administered insulin for six days increased feeding in all control rats and 40% of the TB rats. All insulin-treated groups exhibited equal degrees of hypoglycemia irrespective of anorexia. Basal concentrations of lactate and glucagon were elevated in saline-treated TB rats. Plasma lactate levels were normalized by insulin treatment, whereas glucagon was normalized only in the TB rats that fed to insulin and increased further in TB rats that did not feed to insulin. Elevated hypothalamic tyrosine was reduced in insulin-treated TB rats that ate, and 5-hydroxy-indoleacetic acid was increased further when the rats did not eat. Insulin also blocked anorexia resulting from the intravenous infusion of ammonium salts. Hypothalamic concentrations of tyrosine and tryptophan were increased by the ammonia infusion and reduced significantly in insulin-treated infused rats. These results indicate that insulin treatment can reverse experimental cancer-induced anorexia and hyperammonemia-induced anorexia. Neurochemical changes associated with these treatments are also similar, but not identical.
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PMID:Insulin reverses ammonia-induced anorexia and experimental cancer anorexia. 752 Oct 32

The mouse tumor cell line alpha TC1-6 was used as a model system to examine the post-translational processing of proglucagon. Determination of the mouse preproglucagon cDNA sequence and comparison with the published sequences of rat and human preproglucagons revealed nucleic acid homologies of 89.1 and 84%, respectively, and amino acid homologies of 94 and 89.4%, respectively. Immunohistochemical analyses with antibodies directed against PC2 and glucagon colocalized both the enzyme and substrate within the same secretory granules. PC1 was also immunolocalized in secretory granules. Cells were metabolically labeled with [3H]tryptophan, and extracts were analyzed by reverse-phase high pressure liquid chromatography. Radioactive peptides with retention times identical to those of synthetic peptide standards were recovered and subjected to peptide mapping to verify their identities. To determine the potential role of PC1 and PC2 in proglucagon processing, 3H-labeled proglucagon was incubated in vitro with recombinant PC1 and/or immunopurified PC2. Both enzymes cleaved proglucagon to yield the major proglucagon fragment, glicentin, and oxyntomodulin, whereas only PC1 released glucagon-like peptide-I from the major proglucagon fragment. Neither PC1 nor PC2 processed glucagon from proglucagon in vitro. These results suggest a potential role for PC1 and/or PC2 in cleaving several of the normal products, excluding glucagon, from the mouse proglucagon precursor.
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PMID:Processing of mouse proglucagon by recombinant prohormone convertase 1 and immunopurified prohormone convertase 2 in vitro. 773 Mar 17

Nineteen bulimic women and 22 age-matched controls were randomly assigned to receive 25 g of glucose or a placebo injection under double-blind conditions. Blood samples of glucose, insulin, and glucagon, and psychometric assessments of mood and food cravings were obtained 10 min before, and 0, 5, 10, 20, 30, 45, and 60 min after injection. Blood levels of the large neutral amino acids (LNAAs) tryptophan, tyrosine, leucine, valine, phenylalanine, and leucine were determined at 10 min before and 60 min after the injection. Bulimic subjects were found to report more symptoms of distressed mood throughout the entire monitoring period than controls. Five minutes following glucose ingestion the self-reports of depression, fatigue, anxiety, and bewilderment rose to a level among the bulimic subjects that was above that at baseline, and was higher than that of bulimia nervosa (BN) subjects receiving placebo. No comparable change in mood was observed among controls. Blood glucose levels were correlated with mood in the bulimic group, but not in controls. In addition, the glucose injection induced a heightened urge to binge in the bulimic group (compared to placebo at 10 and 60 min), whereas reducing food cravings (for sweets) in the controls (at 5 min). When collapsed across time and injection condition, the blood glucose level of bulimics was lower than that of controls. There were no differences in insulin response between the groups. The bulimic group was found to have lower baseline levels of blood tryptophan, whereas no differences in the tryptophan/LNAA ratio were observed either at baseline or following glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A double-blind placebo-controlled glucose challenge in bulimia nervosa: psychological effects. 844 64

The studies were performed on cultured TT cells originating from human thyroid medullary carcinoma (i.e., from parafollicular cells of the thyroid). The amount of released calcitonin was dependent upon calcium level in the medium. Moreover, calcitonin secretion might be regulated by medium supplementation with polypeptide hormones. Somatostatin inhibited while glucagon and pentagastrin stimulated calcitonin secretion to t he medium. Calcitonin secretion was also influenced by biogenic amines and their precursors. Dihydroxy-1-phenylalanine and serotonin augmented while 5-hydroxy-1-tryptophan and dopamine inhibited calcium secretion. This, calcitonin secretion may be controlled by different substances present in the healthy organism. This points to a complex control of calcium ion level in the blood.
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PMID:Regulation of calcitonin secretion by thyroid parafollicular cells in vitro. 861 73


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