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 action of Armillaria mellea protease has been evaluated on a number of polypeptide substrates. It has been shown to split the Pro7-Lys8 bonds in both native and oxidised lysine-vasopressin and the Ser11-Lys12 bond in glucagon. No other splits were detected in these substrates. The enzyme also caused extensive degradation of S-carboxymethyl lysozyme, S-carcoxymethyl pepsinogen and oxidised ribonuclease. A. In each case the only new amino-terminal residue to appear was lysine. A. mellea protease was inhibited by the chelating agents 1,10-phenanthroline, alpha, alpha'-bipyridine and imidazole. The pK1 values (negative log10 of concentration required for 50% inhibition) for these three inhibitors were 3.9, 3.4 and 1.1, respectively. Lysine, S-2-aminoethylcysteine and short chain aliphatic amines also proved to be relatively good inhibitors of A. mellea protease while arginine was a poor inhibitor.
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PMID:Specificity and inhibition studies of Armillaria mellea protease. 2 49

The trimerization constants of glucagon at pH 10.6 in 0.76 M K2HPO4 have been calculated from circular dichroism data between 5 and 50 degrees C. The free energy, enthalpy, and entropy of transfer have been evaluated from the current results and published data in 0.20 M phosphate. The free energies of transfer are derived completely from an increase in the entropy of transfer, since the enthalpy of transfer is less favorable at all temperatures. These parameters are compared with those of various model groups and compounds: CH2, peptide, methane, ethane, and the 1--13 N-terminal fragments of ribonuclease. The effects of fluoride and chloride on the self-association of glucagon have been compared with that of phosphate at 25 degrees C. These effects are consistent with the binding of approximately one molecule of salt to the trimer and a systematic decrease in the number of water molecules bound to the trimer compared to the monomer for the series K2HPO4, KF, and KCl.
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PMID:Effects of Hofmeister salts on the self-association of glucagon. 64 94

Interactions of several proteins with glutathione-insulin transhydrogenase (GIT) have been investigated by determining their ability to inhibit degradation of 125I-labeled insulin catalyzed by GIT. The inhibition by every insulin analog (des-Asn-des-Ala-pork insulin, desoctapeptide-pork insulin, des-Ala-pork insulin, pork insulin, proinsulin, and guinea pig insulin) was competitive vs. competitive vs. insulin indicating that they function as alternate substrates. The insulin analogs with the least hormonal activity showed the highest potency as inhigitors of insulin degradation. Whereas native ribonuclease and lysozyme showed little or no inhibition, their scrambled forms (i.e. reduced and randomly reoxidized) showed competitive inhibition with a potency greater than that of insulin. These results suggest that the conformation of the substrate or inhibitor is probably the major factor in determining the specificity for (or binding to) the enzyme. Studies withother peptide hormones showed competitive inhibition with vasopressin and oxytocin and noncompetitive inhibition with glycagon. The inhibition with growth hormone could be either competitive or noncompetitive. The inhibition by glucagon and growth hormone (physiologic antagonists of insulin) could serve as a control mechanism to modulate the activity of enzyme. The following showed very little or no inhibition; the native and scrambled form of pepsinogen, trypsin inhibitor of beef pancreas and of lima bean, C-peptide of pork proinsulin, and heptapeptide (B23-B29) of insulin.
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PMID:Interaction of insulin analogs, glucagon, growth hormone, vasopressin, oxytocin, and scrambled forms of ribonuclease and lysozyme with glytathione-insulin transhydrogenase (thiol: protein-disulfide oxidoreductase): dependence upon conformation. 117 Aug 77

Techniques of in vitro receptor autoradiography were used to visualize binding of 125I-insulin on slices of frozen rat brain. Slide-mounted sections of frozen rat brain were incubated in 0.05 nM porcine 125I-monoiodoinsulin, alone or mixed with 1 microM unlabeled porcine insulin, ribonuclease, or glucagon, for 2 h at 22 degrees C. The labeled brain slices were apposed to LKB Ultrofilm to generate autoradiograms. The method permitted equal access of labeled insulin to both sides of the blood-brain barrier and localization of insulin binding sites in small anatomic regions. Quantitative estimates of specific iodoinsulin binding were made by computer digital image densitometry of the autoradiographic film images. High concentrations of specific binding sites for iodoinsulin were present in the choroid plexus of the lateral (26.9 +/- 2.0 X 10(-3) fmol/mm2), fourth (18.3 +/- 3.0 X 10(-3) fmol/mm2), and third (13.2 +/- 1.5 X 10(-3) fmol/mm2) ventricles (insulin binding is expressed per unit area of autoradiographic image). Binding to the third ventricular choroid plexus was similar to the concentrations observed for liver slices and the external plexiform layer of the olfactory bulb. Specific binding of iodoinsulin in the cingulate cortex and other surrounding regions was less than in choroid plexus. Ribonuclease or glucagon had no measurable effect on binding when mixed with labeled insulin. The results support the hypothesis that the choroid plexus has a high density of receptors for insulin, and suggests that the choroid plexus may be a target of CSF insulin action and/or a site of insulin transport into the CSF.
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PMID:Quantitative autoradiographic evidence for insulin receptors in the choroid plexus of the rat brain. 351 Sep 31

Gabonase, an enzyme which acts on fibrinogen and factor XIII in uniquely thrombin-like ways, was purified to electrophoretic homogeneity from the venom of Bitis gabonica. On sodium dodecyl sulfate-polyacrylamide electrophoresis, the reduced protein behaved as a single chain with Mr = 30,600. The enzyme contains 20.6% carbohydrate, no free sulfhydryl groups and hence, from amino acid analysis, five disulfide bonds. Its extinction coefficient (E1%1cm) at 280 nm is 9.6. Its pI is 5.3. Gabonase has an active serine residue, is inactivated by phenylmethanesulfonyl fluoride, and has an active histidine which reacts with the chloromethyl ketone of tosyl-L-lysine. Its NH2-terminal amino acid sequence (Val-Val-Gly-Gly-Ala-Glu-Cys-Lys-Ile-Asp-Gly-His-Arg-Cys-Leu-Ala-Leu-Leu -Tyr-) is homologous to the B chain of thrombin. The activity of the enzyme is stabilized by calcium ion. It exhibits strong N alpha-p-tosyl-L-arginine methyl esterase activity, hydrolyzes tripeptide nitroanilide derivatives weakly or not at all, and cleaves no peptide bonds in insulin, glucagon, or the S peptide of ribonuclease. Gabonase clots fibrinogen with a specific activity of 45 NIH thrombin-equivalent units/mg, releasing both fibrinopeptides A and B and showing substrate inhibition at fibrinogen concentrations of 3 mg/ml or greater. The enzyme also activates factor XIII. It is not inactivated by either heparin or hirudin.
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PMID:Thrombin-like enzyme from the venom of Bitis gabonica. Purification, properties, and coagulant actions. 352 80

Previous studies have shown that a neutral metallo-endopeptidase purified from rat kidney degrades the B chain of insulin, glucagon, ACTH and, at a markedly slower rate, the A chain of insulin. In contrast the enzyme does not attack native insulin, oxytocin, vasopressin, ribonuclease, albumin or denatured hemoglobin. The current studies demonstrate that the neutral peptidase also degrades the isolated C-peptide of proinsulin and cleaves certain peptide bonds in and near the C-peptide moiety of native proinsulin. Time courses of the formation of fluorescamine-reactive material during digestion of proinsulin and isolated C-peptide with the peptidase were identical. However, structural analysis of the peptidase-digested proinsulin showed that the enzyme does not convert proinsulin to insulin but that the peptidase cleaves one bond, Tyr26-Thr27, in the B chain moiety and five bonds in the C-peptide moiety, producing four split proinsulins. One of the split proinsulins is des-octacosa-peptide (27-54) porcine proinsulin or des-tetracosapeptide (27-50) bovine proinsulin. Each is a derivative of the insulin molecule having an extension of nine residues (ten residues in the case of the derivative from bovine proinsulin) at the N-terminus of A chain and lacking four residues at the C-terminus of B chain. This two chain derivative retains full immunoreactivity with insulin antibodies and exhibits 2.4-times more biological activity (promotion of glycogenesis in primary cultured hepatocytes) than proinsulin and about two-thirds the activity of insulin.
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PMID:Degradation of proinsulin and isolated C-peptide by rat kidney neutral metallo-endopeptidase. 702 23

Treatment of spectrin, insulin, glucagon and ribonuclease with ozone results in covalent cross-linking of these proteins. This cross-linking is not reversed by treatment with dithiothreitol and thus can not be ascribed to -S-S- bond formation. A concomitant O,O'-dityrosine formation is observed by spectrofluorometric analysis of the protein and by amino acid analysis and thin-layer chromatography of hydrolyzed protein samples. It is highly probable that the observed protein cross-linking should be attributed to interpeptide O,O'-dityrosine bonds. Several authors have shown before that oxidation of proteins with horseradish peroxidase and H2O2 also leads to O,O'-dityrosine formation. Peroxidase-induced O,O'-dityrosine formation in galactose oxidase (d-galactose:oxygen 6-oxidoreductase, EC 1.1.3.9) causes a strong increase of enzyme activity. In accordance with these observations ozone treatment of galactose oxidase also leads to O,O'-dityrosine formation with a concomitant 8-fold increase of enzyme activity.
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PMID:Ozone-induced formation of O,O'-dityrosine cross-linked in proteins. 704 79

Differential developmental regulation of pancreas-specific genes has not been reported for the human fetal pancreas. We have therefore undertaken a systematic, quantitative analysis of the transcriptional levels of various genes in the human pancreas at different stages of fetal and postnatal development. Using sensitive ribonuclease protection assays, in situ hybridization, and the polymerase chain reaction, our results indicate the following: 1) Transcriptional levels of insulin and amylin remain lower in the fetal than in the adult pancreas, whereas glucagon and somatostatin mRNA levels are consistently greater after 14 wk gestation than postnatally. These results are in agreement with previous immunohistochemical studies of these gene products. 2) The reg gene exhibits a 20-fold increase in mRNA levels after 16 wk gestation. The gene is expressed exclusively in the acinar cells and does not colocalize with insulin. This restricted exocrine expression does not indicate a direct role for the reg gene in islet development. 3) Glucose transporter 2 and glucokinase mRNA are detectable as early as 13 wk gestation and remain low throughout development. Glucose transporter 1 reaches adult transcriptional levels by 18 wk gestation. The early detection of glucose transporter 2 and glucokinase implies that lack of expression of these "glucose sensor" genes does not account for the known insensitivity of the fetal beta-cells to glucose.
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PMID:Developmental gene expression in the human fetal pancreas. 752 96

Glucagon and glucagon-like peptide-1 (GLP-1) are important regulators of glucose homeostasis, and both are involved in regulating pancreatic islet hormone secretion. Since the sensitivity of the endocrine pancreas to regulatory hormones can be influenced by their receptor number, we have examined the regulation of glucagon receptor and GLP-1 receptor messenger RNA (mRNA) expression in cultured rat pancreatic islets by various factors, including glucose, cAMP, and glucocorticoids. By ribonuclease protection assay we have demonstrated the expression of both glucagon and GLP-1 receptor mRNA in cultured rat islets. We observed a dose-dependent increase in glucagon receptor mRNA expression with increasing glucose concentrations: an approximately 3-fold increase in glucagon receptor mRNA in islets cultured in 22 mM glucose as compared to 3.5 mM glucose. GLP-1 receptor mRNA levels, on the other hand, were not affected by culturing the islets in low glucose concentrations; however, a small, but significant, decrease in GLP-1 receptor mRNA levels was detected when islets were cultured in 20 mM glucose. Forskolin and 3-isobuty-1-methylxanthine, which increase intracellular cAMP levels, caused a 75% reduction in glucagon receptor mRNA expression. Somatostatin 14 and 28, both of which can inhibit intracellular cAMP production, stimulated glucagon receptor mRNA expression by 40% and 75%, respectively. GLP-1 receptor mRNA levels remained unchanged under all conditions that altered intracellular cAMP levels. Finally, in islets cultured in the presence of 10 nM dexamethasone an approximately 50% decrease in both glucagon and GLP-1 receptor mRNA expression was observed. These results indicate that the expression of glucagon and GLP-1 receptor mRNA is differentially regulated in rat pancreatic islets and suggest that regulation of receptor mRNA expression may be an important mechanism for controlling the sensitivity of the islets to glucagon and GLP-1.
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PMID:Regulation of glucagon and glucagon-like peptide-1 receptor messenger ribonucleic acid expression in cultured rat pancreatic islets by glucose, cyclic adenosine 3',5'-monophosphate, and glucocorticoids. 753 5

Glucagon, the pancreatic hormone secreted in response to hypoglycemia, is a key regulator of hepatic glucose production. Since the number of specific glucagon receptors expressed on the cell surface affects the sensitivity of the liver to glucagon, we have examined the regulation of glucagon receptor mRNA levels in cultured primary rat hepatocytes. By ribonuclease protection assay we have identified glucose and intracellular cAMP as regulators of glucagon receptor mRNA expression in cultured rat hepatocytes. We observed a concentration-dependent increase in glucagon receptor mRNA expression when hepatocytes were cultured in the presence of increasing glucose. A 2-fold induction in glucagon receptor mRNA levels was obtained in hepatocytes cultured for 24 h with 22.5 mM glucose as compared with 5.5 mM glucose. Factors such as 3-isobutyl-1-methylxanthine (IBMX), isoproterenol, and forskolin, which are known to raise intracellular cAMP levels, all caused a reduction in glucagon receptor mRNA expression. IBMX alone, IBMX together with isoproterenol, and forskolin reduced glucagon receptor mRNA expression to approximately 25, 10, and 50%, respectively. Glucagon was found to dose dependently decrease glucagon receptor mRNA expression in the hepatocytes with an approximately 70% reduction in response to 100 nM glucagon. Finally, we observed a marked reduction in the number of glucagon binding sites (35% of control) after hepatocytes were cultured with the combination of IBMX and isoproterenol. These results indicate that hepatic glucagon receptor mRNA levels can be regulated by glucose and intracellular cAMP and that this is also reflected at the protein level. Furthermore, the observed effects of cAMP and glucagon suggest that this may be a means by which glucagon can down-regulate its own receptor expression.
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PMID:Regulation of glucagon receptor mRNA in cultured primary rat hepatocytes by glucose and cAMP. 754 Oct 48


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