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

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

The effect of carbohydrate overfeeding on protein metabolism was studied in 11 healthy men. Total urinary nitrogen output during 10 days of carbohydrate overfeeding (1,600 extra kcal/day) decreased 27% relative to nitrogen excretion during 10 days of weight maintenance, indicating protein accretion during over-feeding. However, postabsorptive nitrogen excretion did not change, which means that the positive nitrogen balance associated with overfeeding results from enhanced postprandial nitrogen retention. Overfeeding reduced postabsorptive glucose concentrations 4 +/- 1% and increased glucose production rate 14 +/- 2% and glucose clearance 17 +/- 4%. Overfeeding increased plasma concentrations of insulin, glucagon, and 3,5,3'-triiodothyronine approximately 20%. Alanine and branched-chain amino acid concentrations were increased after overfeeding, but serine, threonine, and asparagine concentrations were reduced. Postabsorptive leucine flux, which is an index of proteolysis, was measured using L-[1-13C]leucine as a tracer. Overfeeding increased leucine flux 13 +/- 2% compared with values after 10 days on a weight-maintenance diet. If it is assumed that overfeeding did not alter the fraction of 13CO2 not recovered in breath, there was no change in the portion of leucine flux that was oxidized. Thus the difference between flux and oxidation, which is a theoretical index of protein synthesis, increased 12 +/- 3% after overfeeding. These data suggest that excess caloric intake, without an increase in protein intake, stimulates post-absorptive proteolysis and protein synthesis.
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PMID:Stimulation of protein turnover by carbohydrate overfeeding in men. 278 3

The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0-5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal-induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia.
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PMID:Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. 289 85


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