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)

N6,O2'-dibutyrylcyclo-3',5'-AMP injected to intact rats alone or in combination with theophylline increases the activity of guanidine acetate methyltransferase (GAMT) in liver and pancreas. Cyclic 3',5'-AMP and its dibutyryl analog administered immediately or two hours after the suturing of common bile duct (SCBD) stimulate the increase of pancreatic GAMT activity 2-3 fold. Glucagon, injected intraabdominally simultaneously with SCBD and administration of theophylline, dramatically increases the theophylline effect on the GAMT activity. The freezing of rat pancreas pretreated witn secretin, a hormone structurally similar to glucagon, results in a 1.5-2-fold increase of creatine synthesis from S-adenosylmethionine and guanidinacetic acid. An hour after glucagon administration to intact rats the GAMT activity of liver increases 9 times. The effect of glucagon is enhanced by insulin. Cycloheximide inhibits the increase of GAMT activity, induced by glucagon or a combination of glucagon and insulin. Experiments on tissue homogenates demonstrate that 3',5'-AMP in concentrations of 10(-8) --10(-2) M does not affect the GAMT activity or to some extent inhibits the enzyme. The homogenate incubation in a medium containing 10(-5) M epinephrine or 10(-7) M caffeine and 5 mM Mg2+ leads to an increase in the GAMT activity. Oligomycin removes the stimulating effects of caffeine and Mg2+ on the enzyme activation. This is probably due to the presence of 3',5'-AMP-dependent protein kinase in the mechanism of GAMT activation by cyclic AMP.
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PMID:[The stimulating effect of cyclic AMP, glucagon and insulin on guanidine acetate-N-methyltransferase activity in rat liver and pancreas]. 17 11

The activity of enzymes of creatin biosynthesis in the rat liver and kidneys has been studied during the postnatal development. The activity of transamidinase of kidneys (E.C. 2.1.4.1.) increases gradually and linearly up to the 20th day after birth, then decreases on the 12th--25th days and increases again up to the level characteristic of the adult organism. The activity of guanidine acetate-N-methyl transferase (E.C. 2.1.1.2.) is rather high during the first days of postnatal development, then decreases and from the 15th day on increases again attaining the maximal level by the 23rd--25th day. The second period of the increase in the enzyme activity begins on the 29th--30th day of postnatal development. The results obtained suggest that the sharp increase of activity of guanidine acetate-N-methyl transferase of the rat liver during the early postnatal development is realized with the participation of cyclic 3',5'-AMP which appears to mediate the glucagon action.
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PMID:[Creatine biosynthesis enzymes in the postnatal development of rats: the role of cyclo-3',5'-AMP and glucagon in the postnatal induction of liver guanidine acetate-N-methyltransferase]. 20 20

Activity of enzymes responsible for creatine biosynthesis (transamidinase, EC 2.1.4.1., and guanidine acetate methyltransferase, EC 2.1.1.2.) was studied in homogenates of pancreas, kidney and liver tissue of mice in normal state and in hereditary muscle dystrophy (129/Re-dy). Simultaneously, the activity of guanidine acetate methyltransferase from liver tissue was studied after addition of glucagon and ardenaline. In normal healthy mice homogenates of liver tissue distinctly increased the activity of guanidine acetate methyltransferase if glucagon and adrenaline were used in physiological concentrations. At the advanced stage of mice hereditary myodystrophy liver homogenates lost their capacity to activate the enzyme after addition of the hormones. The data obtained suggest that adenyl cyclase is impaired in plasmatic membranes of liver tissue, which mediated, using cAMP,the transformation of hormonal signals affecting the intracellular synthesis of creatine.
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PMID:[Creatine biosynthesis in mice with hereditary muscular dystrophy: possible defect in liver plasma membrane adenyl cyclase]. 103 2

Recombinant glucagon was expressed in Escherichia coli as a fusion protein including the glucagon sequence therein as previously reported [Ishizaki et al. (1992). Appl. Microbiol. Biotechnol. 36, 483-486]. We developed a large-scale method for the isolation and purification of recombinant glucagon. After cell disruption, the resultant pellets were solubilized with 2 M guanidine-HCl, to which Staphylococcus aureus V8 protease had been added, and were digested into intermediates composed of 53- and 60-residue peptides containing the glucagon moiety. After the digestion came to an end, the solution was desalted, and the remaining V8 protease was allowed to resume digestion of the intermediates into glucagon, followed by partial purification by S-Sepharose and Sephacryl S-100 chromatographies. The glucagon obtained was found to be not less than 99.5% pure by analytical HPLC. One liter of culture produced about 180 mg of pure glucagon. The amino acid composition and the sequence agreed well with the theoretical values. Radioreceptor assay gave an affinity constant similar to that of pancreatic glucagon, and similar activities in cAMP production and glycogenolysis were also observed. Thus, the recombinant glucagon was confirmed to be biochemically identical with pancreatic glucagon.
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PMID:Recombinant human glucagon: large-scale purification and biochemical characterization. 133 14

Acid-ethanol extracts of fetal bovine pancrease were examined for the presence of beta-endorphin-like immunoreactivity. Gel-filtration analyses revealed the presence of a major large-molecular-weight beta-endorphin immunoreactive species of approximately 20K delta. This molecular form maintained its size upon resubmission to gel filtration in the presence of 6 M guanidine hydrochloride, separated from the bulk of the glucagon immunoreactivity upon ion-exchange chromatography, showed proportional dilution in the beta-endorphin radioimmunoassay, and interacted in a biospecific manner with Concanavalin-A-Sepharose.
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PMID:Beta-endorphin-like immunoreactivity in extracts of the fetal bovine pancreas. Column chromatographic characterizations of a high-molecular-weight immunoreactive species. 632 Dec 78

Synthalin A is a guanidine derivative, chemically related to the antidiabetic drugs of the biguanide group. The effects of this drug have now been studied with respect to pancreatic islet morphology, glucagon release and glucose oxidation of the pancreatic A2-cells using isolated islets from normal and streptozotocin-treated guinea pigs. At 5.5 mmol/l glucose, synthalin A (5-500 micrograms/ml) increased glucagon secretion from isolated normal islets by 2-3 times. The enhanced glucagon release by 5 micrograms/ml of the drug was not suppressed by high concentrations of glucose plus insulin in the medium, whereas exogenous somatostatin markedly counter-acted glucagon release evoked by synthalin A. Addition of synthalin A (5-500 micrograms/ml) to isolated, A2-cells rich islets from streptozotocin-treated animals, suppressed the glucose oxidation rate to less than one third of that obtained in 5.5 mmol/l glucose alone. Glucose oxidation of normal islets was similarly reduced, but to a smaller extent. Light microscopy of islets, cultured for 3 days after exposure (2 hours) to synthalin A, showed vacuolization and other dose-dependent degenerative signs. In conclusion, synthalin A markedly affected islet morphology and stimulated glucagon secretion of isolated guinea pigs islets. Furthermore, the simultaneous inhibition, by synthalin A, of glucose oxidation of the A2-cell rich islets supports the concept of a glucose-mediated regulation of glucagon release, via the energy-yielding metabolism of the A2-cell.
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PMID:Effects of the biguanide synthalin A on the pancreatic A2-cell of the guinea pig. 635 26

In an attempt to determine the ability of rat submaxillary glands to synthesise glucagon via protein intermediates, isolated cells from these glands were incubated in vitro with 3H-L-tryptophan and the acid-ethanol extracts of the cells were purified on Bio-Gel P-30 columns. Aliquots of the eluates were incubated with a C-terminal glucagon antiserum (30K) and the radioactivity bound to the glucagon antibody appeared to be distributed among proteins of Molecular weight greater than 40.14 and 3.5 Kdaltons. A similar elution pattern was obtained in the presence of urea (7 mol/l) and guanidine hydrochloride (6 mol/l). To determine the molecular weight of the immunoreactive material eluting before the 3.5 Kdalton polypeptide, aliquots of the cell extracts were immunoprecipitated and analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Polypeptides of 125.8, 63.1, 42.6 and 14.4 Kdaltons were obtained. These polypeptides incorporate more radioactive tryptophan with increase in the time of incubation. Pulse-chase experiments with unlabelled tryptophan, cycloheximide-treatment of isolated cells and limited tryptic digestion of the larger glucagon immunoreactive component, transform it into a 3.5 Kdalton polypeptide with immunological characteristics indistinguishable from pancreatic glucagon. These results suggest that the larger molecule contains glucagon and thus may serve as a precursor or an intermediate of extrapancreatic glucagon biosynthesis.
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PMID:Evidence of glucagon biosynthesis involving protein intermediates in rat salivary glands. 651 May 94

High molecular weight glucagon immunoreactive material, obtained by gel-filtration (in the presence of 6 M guanidine hydrochloride) of fetal bovine pancreatic extracts, was tritiated by reductive methylation. Concanavalin-A-Sepharose column chromatography of the radiolabeled preparation yielded a discrete Concanavalin-A-reactive, alpha-methyl-mannoside-displaceable radioactive peak, coinciding with the glucagon immunoreactive peak. Submission of the Con-A-reactive material to wheat germ agglutinin-Sepharose column chromatography yielded a lectin-reactive, N-acetyl-glucosamine-displaceable radioactive peak, coinciding with the glucagon immunoreactive peak. The tritiated Con-A-reactive component interacted specifically with anti-glucagon antibodies. Sephacryl S-200 gel-filtration (in the presence of guanidine hydrochloride) dissociated a approximately 40 kDa radioactive species from the antibody-antigen complex. These data provide direct evidence for the existence of a large molecular weight glycosylated glucagon-related protein species from the fetal bovine pancreas.
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PMID:Characterization of a chemically tritiated large molecular weight glucagon immunoreactive protein species by lectin-affinity column chromatography and reaction with anti-glucagon antibodies. 654 29

A 54-year-old woman presented with extremely fluctuating and symptomatic blood glucose levels. Very high levels of somatostatin and low levels of insulin, C-peptide, gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) in peripheral blood were constantly present. A benign somatostatinoma was localized by meta-iodobenzyl guanidine iodine 123 (MIBG-I(123)) scintigraphy and successfully removed encapsulated in an ovarian teratoma. The patient made a complete recovery. The case described is unique with regard to clinical symptomatology and anatomic localization of the tumor.
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PMID:Case report: somatostatin producing teratoma, causing rapidly alternating extreme hyperglycemia and hypoglycemia, and ovarian somatostatinoma. 1220 Jul 64

The proprotein convertases are believed to be responsible for the proteolytic maturation of a large number of peptide hormone precursors. Although potent furin inhibitors have been identified, thus far, no small-molecule prohormone convertase 1/3 or prohormone convertase 2 (PC2) inhibitors have been described. After screening 38 small-molecule positional scanning libraries against recombinant mouse PC2, two promising chemical scaffolds were identified: bicyclic guanidines, and pyrrolidine bis-piperazines. A set of individual compounds was designed from each library and tested against PC2. Pyrrolidine bis-piperazines were irreversible, time-dependent inhibitors of PC2, exhibiting noncompetitive inhibition kinetics; the most potent inhibitor exhibited a K(i) value for PC2 of 0.54 microM. In contrast, the most potent bicyclic guanidine inhibitor exhibited a K(i) value of 3.3 microM. Cross-reactivity with other convertases was limited: pyrrolidine bis-piperazines exhibited K(i) values greater than 25 microM for PC1/3 or furin, whereas the K(i) values of bicyclic guanidines for these other convertases were more than 15 microM. We conclude that pyrrolidine bis-piperazines and bicyclic guanidines represent promising initial leads for the optimization of therapeutically active PC2 inhibitors. PC2-specific inhibitors may be useful in the pharmacological blockade of PC2-dependent cleavage events, such as glucagon production in the pancreas and ectopic peptide production in small-cell carcinoma, and to study PC2-dependent proteolytic events, such as opioid peptide production.
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PMID:Synthetic small-molecule prohormone convertase 2 inhibitors. 1907 44


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