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)

To further investigate the regulation of glucagon biosynthesis in mammalian A2-cells, we have studied the incorporation of [3H]-tryptophan into acid alcohol extracts of isolated pancreatic islets of guinea pig and mouse. Gel chromatography on Sephadex G-50 indicated that labelled proteins, migrating either with the void volume (peak I) or in region (peak II) between the void volume and the insulin marker, were formed during a 6h incubation of the islets. However, a period of at least two days in tissue culture was required before the islets showed any significant accumulation of labelled protein eluting in a position corresponding to that of pancreatic glucagon (peak III). Addition of glucose (16.7 mM) enhanced the incorporation into all chromatograph fractions during the culture period. Binding of gel chromatographed proteins Sepharose coupled anti-glucagon antibodies indicated that both guinea pig and mouse islets contained only small amounts of labelled, immunoreactive proteins eluting with either peak I or peak II. However, proteins eluting with peak III contained 6-8 times more lbelled, immunoreactive material than any of the other peaks. Total glucagon immunoreactivity was abundant in peaks I and II but less evident in peak II. The results of pulse-chase experiments provided no convincing evidence for a precursor-product relationship between larger proteins and glucagon. However, the heterogeneity of the putative precursor pool, as evidenced both by SDS-polyacrylamide gel electrophoresis and by the low immune binding, might have masked a conversion process. The combined data show that glucagon is, indeed, synthesized in isolated islets of guinea-pig and mouse, but that this process occurs slowly.
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PMID:Glucagon biosynthesis in isolated pancreatic islets of mice and guinea pigs. 699 3

Pieces of human salivary glands were homogenised with acid-ethanol or acid-saline solutions immediately after surgical removal. With both extraction procedures the immunoreactive glucagon (IRG) content in the submaxillary glands was greater than in parotid glands as determined with a C-terminal reactive glucagon antiserum (30K). Higher amounts of IRG were determined in acid-saline extracts of submaxillary (18.5 +/- 2.5 VS 8.9 +/- 1.2 ng/g wet weight) and parotid (3.5 +/- 0.3 VS 2.9 +/- 0.3 ng/g wet weight) glands compared with concentrations obtained with acid-ethanol extracts. IRG material extracted with the latter procedure has similar immunological and biological characteristics as pancreatic glucagon. After fractionation of the acid-ethanol extracts on P-30 columns or gel electrophoresis, an immunoreactive peak of 3500 daltons was always obtained. Arginine, ephinephrine and low glucose concentrations stimulated glucagon release from both salivary glands. Active glucagon biosynthesis by these glands was established by the incorporation of 3H-L-tryptophan into a 3500 daltons polypeptide with specific immune reaction with 30K antiserum. These findings indicate that human salivary glands represent a source of extrapancreatic glucagon in man and may therefore contribute to the circulating levels of this hormone.
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PMID:Synthesis and release of glucagon by human salivary glands. 699 16

The conversion of proglucagon and proinsulin by secretory granules isolated from both prelabeled and unlabeled anglerfish islets was investigated. Either granules isolated from tissue labeled with [3H]tryptophan and [14C]isoleucine or [35S]cysteine, or lysed granules from unlabeled tissue to which exogenously labeled prohormones had been added were incubated under various conditions. Acetic acid extracts of these granule preparations were analyzed for prohormone and hormone content by gel filtration. Both prelabeled and lysed, unlabeled secretory granules converted radiolabeled precursor peptides (Mr 8,000-15,000) to labeled insulin and glucagon. The accuracy of the cleavage process was established by demonstrating comigration of products obtained from in vitro cleavage with insulin and glucagon extracted from intact islets using electrophoresis and high-pressure liquid chromatography (HPLC). The pH optimum for granule-mediated conversion was found to be in the range of pH 4.5-5.5. Conversion of both proglucagon and proinsulin by secretory granules was significantly inhibited in the presence of antipain, leupeptin, p-chloromercuribenzoate (PCMB) or dithiodipyridine (DDP) but not chloroquine, diisopropyl fluorophosphate, EDTA, p-nitrophenyl guanidinobenzoate, soybean trypsin inhibitor, or N-p-tosyl-L-lysine chloromethyl ketone HCl. The inhibitory action of PCMB and DDP was reversed in the presence of dithiothreitol. Both membranous and soluble components of the secretory granules possessed significant converting activity. HPLC and electrophoretic analysis of cleavage products demonstrated that the converting activities of the membranous and soluble components were indistinguishable. The amount of inhibition of proinsulin and proglucagon conversion caused by 600 micrograms/ml porcine proinsulin was significantly lower than that caused by the same concentration of unlabeled anglerfish precursor peptides. These results indicate that the proinsulin and proglucagon converting enzyme(s) in the anglerfish pancreatic islet is a unique intracellular thiol proteinase(s) that may be granule membrane-associated and may require the presence of prohormone sequences in addition to the dibasic residues at cleavage sites for substrate recognition and/or binding.
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PMID:Characterization of proinsulin- and proglucagon-converting activities in isolated islet secretory granules. 702 70

Because the supplementation of pyridoxine (vitamin B6) improves the glucose tolerance in gestational diabetes and adult onset diabetes, pyridoxine deficiency has been considered to be one of the factors that cause diabetes mellitus. We produced pyridoxine deficient rats by giving pyridoxine-free food with deoxypyridoxine which competitively the activity of pyridoxal phosphate. In these pyridoxine deficient rats plasma insulin during the glucose tolerance test was significantly low as compared with controls. In vitro experiments of pancreas perfusion showed that secretion of insulin and glucagon was impaired in the pyridoxine deficiency. Since the restriction of diet-calorie caused a decrease in arginine-induced secretion of insulin and glucagon from the isolated pancreas, the impairment of the endocrine pancreas may depend on malnutrition. Pyridoxine deficiency is surely one of the factors that impair the endocrine pancreas by multifactorial derangement of metabolism besides the tryptophan-nicotinic acid pathway.
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PMID:The endocrine pancreas in pyridoxine deficient rats. 703 87

The contribution of hyperammonemia to plasma amino acid imbalance in patients with liver disease was assessed in 10 subjects with chronic hepatitis and in 17 advanced cirrhotics. Insulin, glucagon, and plasma amino acids were determined both in the basal state and 45 min after oral ammonium chloride, at doses used in the ammonia-tolerance test. In cirrhotics, ammonia increased to 3 times basal values, in association with a rise in insulin and, more marked, in glucagon. Aromatic amino acids and free tryptophan further increased, while a significant fall in branched-chain amino acids and glutamate was observed. The increase in ammonia levels strongly correlated with the increase in glucagon (r = 0.707). Two patients, with large esophageal varices, showed signs of disturbed consciousness, in association with a marked rise in ammonia and in the ration of free tryptophan to the sum of neutral amino acids. In patients with chronic hepatitis, whose ammonia levels rose slightly, minor variations in pancreatic glucoregulatory hormones and plasma amino acids were observed, as also happened in 10 healthy subjects following ammonium chloride ingestion. Our data fit with the hypothesis that the plasma amino acid imbalance of cirrhotics may be partly due to ammonia-induced changes in pancreatic hormones.
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PMID:Ammonia-induced changes in pancreatic hormones and plasma amino acids in patients with liver cirrhosis. 704 53

A correlation between the secondary structure of glucagon determined by circular dichroism and its dynamic behaviour as obtained from picosecond fluorescence anisotropy is demonstrated. The CD data show that the percentage of alpha-helix decreases with increasing temperature, but the rotational relaxation time of the glucagon increases with temperature. These observations suggest that the protein's shape changes with temperature in such a way that its volume is larger at 38 degrees C than at 5.5 degrees C. The fluorescence anisotropy of glucagon decays biexponentially at each temperature studied and at 26 degrees C the rotation lifetimes are 1670 and 307 ps at pH 10.2 and 2147 and 517 ps at pH 2.2. It is proposed that the shorter decays are due to the restricted motion of the single tryptophan residue while rotation of the whole protein is responsible for the longer decays. The calculated rotational diffusion coefficient, Dw, of the tryptophan residue is much smaller, (ie. has a larger apparent volume) than that of a free tryptophan in solution. The hydrophobic interactions between residues Phe-22 to Leu-26 are probably responsible for the larger apparent volume in the protein compared to solution and will stabilize this part of the protein. The rotational diffusion of aggregated glucagon is also discussed.
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PMID:Secondary structure and dynamics of glucagon in solution. 715 Jun 8

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


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