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)

At the initial phase of cell differentiation in mouse neuroblastoma (N18) induced by dibutyrylcyclic AMP (dbcAMP), an additional site of histone H1 was extensively phosphorylated. Forskolin and various phosphodiesterase inhibitors also induced both cell differentiation and H1 phosphorylation at the identical site. The phosphorylation preferentially occurred in a single H1 subtype (H1c) among the five (H1a-e) fractionated by high performance liquid chromatography. The three H1 subtypes of N18 (H1c, H1d, and H1e) were phosphorylated in vitro, and their amino acid sequences of the phosphopeptides were identical to the known sequence of rabbit H1 peptides containing a serine 37 residue. However, the amount of H1a and H1b phosphorylations was negligible. The serine residue was replaced by threonine residue in H1a, and H1b did not have a homologous peptide. The tryptic phosphopeptides of H1 in N18 were identical to that in rat liver H1 induced by glucagon (Langan, T.A. (1969) Proc. Natl. Acad. Sci. USA 64, 1276-1283). The results indicate that 1) the response of H1 subtypes to cAMP-dependent protein kinase in vivo and in vitro is H1 subtype-specific, and 2) the H1c phosphorylation may play an important role in the restrictive area of chromatin in both cell differentiation and hormonal stimulation mediated by cAMP.
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PMID:Subtype-specific cyclic AMP-dependent histone H1 phosphorylation at the differentiation of mouse neuroblastoma cells. 169 Jul 30

An amino-terminal histidyl structure (His1) is characteristic of most peptides in the glucagon superfamily. An assay for His1 peptides performed by amino-terminal amino acid sequencing was used to screen venom from the Gila monster lizard, Heloderma horridum. Two His1 peptides were identified: helospectin and a new His1 peptide that has been named exendin-3 to indicate that it is the third peptide to be found in an exocrine secretion of Heloderma lizards which has endocrine activity, the first two being helospectin (exendin-1) and helodermin (exendin-2). In the lot of H. horridum venom tested, exendin-3 was 5-10-fold more abundant in molar concentration than helospectin. The structure of exendin-3 was analyzed by amino acid sequencing and mass spectrometry. Exendin-3 is a 39-amino acid peptide with a mass of 4200. It contains a carboxyl-terminal amide and has a strong homology with secretin at its amino-terminal 12 amino acids. The complete structure of exendin-3 is His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala- Val-Arg - Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro- Ser- amide. It is 32 and 26% homologous with helospectin and helodermin, respectively. It has greatest homology with glucagon (48%) and human glucagon-like peptide-1 (50%). Exendin-3 (3 microM) stimulated increases in cellular cAMP and amylase release from dispersed guinea pig pancreatic acini.
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PMID:Purification and structure of exendin-3, a new pancreatic secretagogue isolated from Heloderma horridum venom. 170 Jul 85

Endosomes have recently been identified as one major site of glucagon degradation in intact rat liver. In this study, a cell-free system has been used to assess the role of ATP-dependent acidification in endosomal glucagon degradation and identify the glucagon products generated. Percoll gradient fractionation of Golgi-endosomal fractions prepared 10-30 min after injection of [125I]iodoglucagon showed a time-dependent shift of the radioactivity towards high densities. Regardless of time, the radioactivity was less precipitable by trichloroacetic acid (Cl3Ac) at high densities than at low densities. Chloroquine treatment slightly increased the density shift of the radioactivity and decreased its Cl3Ac-precipitability throughout the gradient. Incubation of endosomal fractions containing [125I]iodoglucagon in 0.15 M-KCl at 30 degrees C resulted in a time- and pH-dependent generation of Cl3Ac-soluble radioactivity, with a maximum at pH 4 (t1/2, 7 min). At pH 5, 1,10-phenanthroline, bacitracin and p-chloromercuribenzoic acid partially inhibited [125I]iodoglucagon degradation. At pH 6-7, ATP stimulated [125I]iodoglucagon degradation by 5-10-fold and caused endosomal acidification as judged from Acridine Orange uptake. The effects of ATP were inhibited by chloroquine, monensin, N-ethylmaleimide and dansylcadaverine. Poly(ethylene glycol) (PEG) precipitation of the radioactivity associated with endosomes showed that lowering the pH below 5.5 caused dissociation of the glucagon-receptor complex, and that, regardless of incubation conditions, all degraded [125I]iodoglucagon diffused extraluminally. On h.p.l.c., at least three products less hydrophobic than [125I]iodoglucagon were identified in incubation mixtures along with monoiodotyrosine. Radiosequence analysis of the products revealed one major cleavage located C-terminally to Tyr-13 and two minor cleavages affecting Thr-5-Phe-6 and Phe-6-Thr-7 bonds. It is concluded that glucagon degradation in liver endosomes is functionally linked to ATP-dependent endosomal acidification and involves several cleavages in the glucagon sequence.
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PMID:Degradation of glucagon in isolated liver endosomes. ATP-dependence and partial characterization of degradation products. 174 49

A microassay was developed to measure the binding of the labelled monoiodinated analogue [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-methyltyrosine, 4-threonine, 8-ornithine, 9-125I-tyrosylamide]vasotocin [125I-d(CH2)5[Tyr (Me)2, Thr4, Tyr-NH(2)9]OVT] to isolated nephron segments microdissected from collagenase-treated rat kidneys. When determined using 1.7 nM labelled ligand at 4 degrees C, specific binding sites (expressed at 10(-18) mol 125I-d(CH2)5[Tyr (Me)2, Thr4, Tyr-NH(2)9]OVT bound/mm tubule length) were found in medullary thick ascending limbs (MTAL), 1.67 +/- 0.49; cortical thick ascending limbs, 2.20 +/- 0.80; cortical collecting ducts, 2.39 +/- 0.86; outer medullary collecting ducts (OMCD), 2.54 +/- 0.53 and inner medullary collecting ducts, 5.33 +/- 0.40, whereas no specific binding could be detected in glomeruli and proximal tubules. Specific 125I-d(CH2)5[Tyr (Me)2, Thr4, Tyr-NH(2)9]OVT binding to OMCD was saturable with incubation time and reversible after elimination of free labelled ligand (the association and dissociation rate constants at 4 degrees C were 1.06 x 10(7) M-1 min-1 and 1.95 x 10(-2) min-1 respectively). The stereospecificity of MTAL and OMCD binding sites was assessed in competitive experiments revealing the following recognition pattern for a series of eight vasopressin analogues:dDAVP greater than AVP greater than d(CH2)5-[Tyr (Me)2, Thr4, Tyr-NH(2)9]OVT = AVT = OT greater than d(CH2)5[Tyr(Me)2]AVP = [Thr4, Gly7]OT greater than [Phe2, Orn8]VT, whereas pharmacological concentrations of insulin and glucagon did not impair radioligand binding. These results indicate that the detected labelled binding sites might correspond mainly to physiological V2 vasopressin receptors.
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PMID:Receptors for neurohypophyseal hormones along the rat nephron: 125I-labelled d(CH2)5[Tyr(Me)2, Thr4, Orn8, Tyr-NH(2)9] vasotocin binding in microdissected tubules. 183 Mar 90

The effects of glucagon deficiency and excess on plasma leucine, lysine, and alanine were examined in six healthy young adult men, with primed continuous infusions of L-[1-13C]- or L-[5,5,5-2H3]leucine, L-[alpha-15N]-lysine, and L-[3-13C]alanine for 150 min before and during 210 min of either a glucagon-deficient euglycemic state (experiment 1), a basal glucagon state (experiment 2), or a glucagon-excess state (experiment 3). Steady-state plasma hormone levels were achieved by infusion of somatostatin (250 micrograms/h) and insulin (0.07 mU.kg-1.min-1), without (experiment 1) or with an infusion of glucagon at 0.7 ng.kg-1.min-1 (experiment 2) or 2.5 ng.kg-1.min-1 (experiment 3). Plasma branched-chain amino acid (AA) concentrations did not change with altered glucagon status, whereas significant differences were observed for plasma lysine, alanine, glycine, serine, threonine, proline, tyrosine, citrulline, and ornithine levels (0.05 greater than P greater than 0.001). Plasma leucine, lysine, and alanine fluxes and the rate of de novo alanine synthesis showed no significant changes with either glucagon deficiency or excess. These findings lead to the conclusion that glucagon-induced alterations in plasma AA profiles are not due to changes in the rate of appearance of AA from peripheral tissues but rather a consequence of changes in the fate of AA within the splanchnic region.
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PMID:Plasma amino acid kinetics during acute states of glucagon deficiency and excess in healthy adults. 196 9

The chelonians occupy an important position in phylogeny representing a very early branching from the ancestral reptile stock. Hormonal polypeptides in an extract of the pancreas of the red-eared turtle were purified to homogeneity by reversed phase HPLC and their primary structures were determined. Turtle insulin is identical to chicken insulin. Turtle glucagon differs from chicken glucagon by the substitution of a serine by a threonine residue at position 16 and from mammalian glucagon by an additional substitution of an asparagine by a serine residue at position 28. Turtle pancreatic somatostatin is identical to mammalian somatostatin-14. The crocodilians are phylogenetically much closer to the birds than are the chelonians. Alligator insulin, however, contains three amino acid substitutions relative to chicken insulin. Thus, caution is required when inferring phylogenetic relationships based upon a comparison of amino acid sequences of homologous peptides.
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PMID:Isolation and structural characterization of insulin, glucagon and somatostatin from the turtle, Pseudemys scripta. 197 47

Fasting concentrations, clearance of exogenous infused amino acids, and lean body mass were studied in a patient with glucagonoma syndrome (fasting glucagon = 380 pmol/l, normal range 15-45 pmol). The fasting concentrations of all amino acids were reduced. The clearances of alanine, arginine, glycine, isoleucine, leucine, lysine, methionine, proline, serine, threonine, and tyrosine were increased. The urea synthesis rate during amino acid infusion was 27 mumols/kg per minute (normal range 20-24 mumols/kg per minute). The lean body mass of the patients was reduced to 59% of the expected value. It is suggested that the weight loss of patients with glucagonoma syndrome is partly due to increased hepatic conversion of amino acid nitrogen to urea nitrogen, resulting in decreased blood amino acid concentration, and secondary to this, organ protein catabolism, as shown by the decreased lean body mass.
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PMID:Increased amino acid clearance and urea synthesis in a patient with glucagonoma. 216 78

The amino acid sequence of chymodenin, a hormone-like peptide from porcine duodenum is reported. The molecule is known to rapidly alter the proportions of digestive enzymes secreted by the rabbit pancreas in vivo and in vitro, by selection of the specific intra-pancreatic source from which the preset mixture of digestive enzymes is secreted. The sequence is identical to that of cytochrome C-oxidase peptide VII (cCoVII) from bovine heart, with the exception of a substitution of threonine for alanine at position 6 and a second substitution of alanine for threonine at position 71. Disulfide bridges link positions 29-64 and 39-53. cCoVII-chymodenin has a pentapeptide (-Ala-Glu-Gly-Thr-Phe-) near the carboxy-terminus which is immediately preceded by an -Arg-Arg- sequence in the porcine and bovine sequences of cCoVII. This peptide is identical to a pentapeptide found close to the amino terminus of the hormones gastric inhibitory peptide (GIP) and glucagon-like peptide I. The identity to cCoVII means chymodenin as isolated is itself unlikely to be a gastrointestinal hormone. However, the partial commonality of sequence with the glucagon-secretin family immediately adjacent to a pro-hormone-like activation site, and the specific actions on the exocrine pancreas, means that the molecule probably mimics the natural actions of an as-yet uncharacterized member of the glucagon family, which exerts a unique action on exocrine pancreatic secretion.
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PMID:The amino acid sequence of chymodenin, a hormone-like peptide from porcine duodenum, is identical to cytochrome C-oxidase, peptide VII. 217 Oct 45

To determine the effect in normal subjects of small variations of insulin and glucagon on plasma aminoacids concentrations we suppressed endocrine pancreas secretion with somatostatin and measured aminoacids levels during a sequential insulin infusion in the absence (control test, low glucagon level) or in the presence (normal glucagon concentration) of a replacement glucagon infusion. Insulin infusion rates were 0.05, 0.09, 0.15 and 0.30 mU.kg-1.min-1 during the control test and 0.09, 0.15, 0.30 and 0.40 mU.kg-1.min-1 during the replacement test. During the control test, glucagon decreased (p less than 0.01) and insulin levels were successively 8.2 +/- 0.4, 10.1 +/- 0.7, 11.9 +/- 0.14 and 18.5 +/- 0.8 mU.l-1. The only effect on insulin was to decrease branched-chain aminoacids (BCAA). BCAA were inversely related to insulinemia (p less than 0.01). A significant decrease was obtained for an insulin level of 11.9 +/- 0.4 mU.l-1, a value intermediate between those decreasing glycerol (10.1 +/- 0.7 mU.l-1) and stimulating total body glucose uptake (18.5 +/- 0.8 mU.l-1). During the test with glucagon replacement glucagon was maintained at its initial value. Insulin levels were successively 8.3 +/- 0.3, 11.9 +/- 0.3, 19.7 +/- 0.6 and 26.7 +/- 0.5 mU.l-1. Insulin decreased always BCAA but also threonine, proline, tyrosine, methionine and total aminoacid levels. BCAA were always inversely related to insulin levels (p less than 0.01) but the slope of the relationship was modified and more insulin was needed to decrease BCAA concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of small variations in insulin and glucagon levels on plasma aminoacids concentrations. 256 20

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase is the limiting enzyme step in cholesterol formation in mammalian liver and other tissues. It is a glycoprotein of 97,000 daltons embedded in the endoplasmic reticulum with a long cytoplasmic extension that is the site of catalytic conversion of HMG CoA to mevalonate. The enzyme is subject to both long-term (induction/repression; degradation) and short-term control (reversible phosphorylation) mediated by endocrine signaling (insulin, glucagon) and through negative feedback by metabolic products of mevalonate (e.g., cholesterol). The catalytic capacity of microsomal reductase falls rapidly in the presence of several protein kinases (reductase kinase, protein kinase-C, calmodulin-dependent protein kinase). Activity is restored with various protein phosphatases. Increased phosphorylation of reductase in intact cells after addition of glucagon or mevalonate is followed by enhanced degradation of the enzyme. In an in vitro model system, phosphorylated, native microsomal reductase is more rapidly cleaved by the calcium-dependent, neutral protease calpain than the dephosphorylated from of reductase. Our present research which centers on the mechanism of the in vitro model system is reviewed. Calpain in the presence of Ca2+ cleaves the cytosolic domain of phosphorylated 97 kDa reductase at two points giving rise to two fragments of nearly the same size that appear as a 52-56,000 dalton doublet by electrophoresis and immunoblotting. In the same system native reductase labeled with [gamma-32P]ATP generates a doublet with 32P solely in the upper (heavier) band. This indicates that serine phosphorylation sites lie between the two calpain cleavage loci. These are positioned in the "linker" region of the long carboxy-terminal cytosolic domain near the membrane. This segment possesses five invariant serine residues and two PEST sequences (constellations of proline, glutamate, serine and threonine) that are characteristic of proteins with short half-lives. If phosphorylation of HMG CoA reductase is confined to the linker region, we must look to this domain in order to interpret the resulting conformational changes that markedly influence reductase catalytic activity and prepare the enzyme for degradation.
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PMID:Phosphorylation and degradation of HMG CoA reductase. 262 76


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