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)

Tryptophan uptake, hydroxylation, and decarboxylation in isolated synaptosomes were studied to assess how their properties may determine the rate of serotonin synthesis in the presynaptic nerve terminals of the brain. Simultaneous measurements of the rates of uptake, hydroxylation, and decarboxylation in the presence and absence of various inhibitors showed that tryptophan hydroxylase is rate-limiting for serotonin synthesis in this model system. There was significant direct decarboxylation of tryptophan to tryptamine. Measurement of tryptophan hydroxylase flux with varying internal concentrations of tryptophan allowed the determination of the Km of tryptophan hydroxylase in synaptosomes for tryptophan of 120 +/- 15 microM. Depolarisation of synaptosomes with veratridine caused both a reduction in the internal tryptophan concentration and an apparent activation of tryptophan hydroxylase. This activation did not occur in the absence of Ca2+ or in the presence of trifluoperazine. Synaptosomal serotonin synthesis and brain stem-soluble tryptophan hydroxylase were inhibited by low concentrations of noradrenaline or dopamine. Dibutyryl cyclic AMP, glucagon, insulin, and vasopressin were observed to have no effect on tryptophan uptake or hydroxylation in synaptosomes.
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PMID:Tryptophan uptake and hydroxylation in rat forebrain synaptosomes. 669 97

The interaction of glucagon and phenylalanine mediated by the OH . radical causes formation of higher molecular weight products of glucagon and phenylalanine, loss of amino acid residues in glucagon, and formation of adducts of glucagon and phenylalanine. The relative yields of these products depend upon the molar ratio of phenylalanine to glucagon in solution. At low ratios, glucagon aggregation and loss of amino acid residues predominate; at high ratios, the formation of phenylalanine dimers (and possible trimers and tetramers) predominates. The formation of adducts reaches a maximum at a phenylalanine:glucagon molar ratio of 3-4, and then decreases gradually, as the molar ratio increases, but is still discernible even at high molar ratios. Mechanisms for the formation of adducts are suggested. The influence of the primary aqueous radical intermediates, OH., H., and e-aq, on adduct formation has been evaluated for several different amino acids by irradiating in the presence of specific radical scavengers. For the aromatic amino acids (phenylalanine, tryptophan, and tyrosine), OH. is considerably more effective than e-aq for mediating adduct formation, whereas for histidine and methionine, these primary radicals are equally effective.
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PMID:Gamma-radiation-induced interactions between amino acids and glucagon. 669 44

To show that glucagon, glucagonlike immunoreactivity (GLI), and insulin are synthetized by organs other than the pancreas and the gastrointestinal tract, different rat tissue acid-ethanol extracts were obtained and analyzed by immunoassay using specific antisera. Significant amounts of glucagon were found in the gastrointestinal tract (44.77 +/- 5.4 ng), salivary glands (1.50 +/- 0.17 ng), thymus (2.80 +/- 0.46 ng), thyroid (0.25 +/- 0.02 ng), and adrenal glands (0.25 +/- 0.06 ng). Whereas GLI appeared in the gut mucosa, adrenal and salivary glands, genuine insulin was detected only in the pancreas. Aliquots of the tissue extracts, fractionated on Bio Gel P 30 columns, gave a 3,500 mol wt immunoreactive (30 K) peak that behaved as pancreatic glucagon on acrylamide gel electrophoresis and displaced 125I-labeled glucagon previously bound to its hepatic receptors. Arginine, epinephrine, and low glucose concentrations stimulated glucagon release from parotid, thymus, and thyroid. Active glucagon biosynthesis by these organs was established by the incorporation of L-[3H]tryptophan into a 3,500 mol wt polypeptide with specific immune reaction with 30 K antiserum. These results suggest that different rat tissues can contribute to the circulating levels of glucagon and GLI and therefore to metabolic homeostasis.
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PMID:Tissue distribution of glucagon, glucagonlike immunoreactivity, and insulin in the rat. 698 65

Monolayer cell cultures from pancreatic islets of aging 129/J strain diabetes (db3J/db3J) and lean littermate control mice were tested for differences in glucagon and insulin secretion in either serum-free Eagle's minimal essential medium (MEM) or Dulbecco's modified minimal essential medium (DMEM). There was a highly significant (p less than 0.0001) main effect of genotype and type of culture medium on glucagon secretion with time. Thus, although numbers of A-cells were not demonstrably increased in db3J/db3J cultures in DMEM, mean medium glucagon levels increased 2.7-, 18-, and 32-fold above littermate normal culture levels at days 4, 6, and 8 respectively. In MEM, the two populations could not be discriminated on the basis of glucagon secretion. By contrast, insulin secretion over culture days showed a highly significant (p less than 0.0001) dependence on genotype, but not type of medium, with the B-cell enriched db3J/db3J preparations secreting between 20 and 30 times as much insulin as controls in both medida. Analysis revealed that the heightened secretory responsiveness of mutatn A-cells in DMEM as compared to MEM was primarily elicited by the elevated DMEM amino acid concentration and specifically lysine (0.8 mmol/l in DMEM versus 0.4 mmol/l in MEM). In pulse-chase experiments using 14 day db3J/db3J cultures, incorporation of 3H-tryptophan into protein that eluted from Biogel P-10 columns in the native glucagon peak indicates that DMEM stimulated glucagon biosynthesis as well as secretion. This study reveals an augmented sensitivity of db3J/db3J A-cells to stimulation by basic amino acids in long-term culture.
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PMID:A new mutation (db3J) at the diabetes locus in strain 129/J mice. II. Studies of pancreatic alpha cell function in culture. 699 70

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


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