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)

We reported that glucagon and phenylephrine decrease hepatocyte GSH by inhibiting gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH synthesis (Lu, S.C., J. Kuhlenkamp, C. Garcia-Ruiz, and N. Kaplowitz. 1991. J. Clin. Invest. 88:260-269). In contrast, we have found that insulin (In, 1 microgram/ml) and hydrocortisone (HC, 50 nM) increased GSH of cultured hepatocytes up to 50-70% (earliest significant change at 6 h) with either methionine or cystine alone as the sole sulfur amino acid in the medium. The effect of In occurred independent of glucose concentration in the medium. Changes in steady-state cellular cysteine levels, cell volume, GSH efflux, or expression of gamma-glutamyl transpeptidase were excluded as possible mechanisms. Both hormones are known to induce cystine/glutamate transport, but this was excluded as the predominant mechanism since the induction in cystine uptake required a lag period of greater than 6 h, and the increase in cell GSH still occurred when cystine uptake was blocked. Assay of GSH synthesis in extracts of detergent-treated cells revealed that In and HC increased the activity of GCS by 45-65% (earliest significant change at 4 h) but not GSH synthetase. In and HC treatment increased the Vmax of GCS by 31-43% with no change in Km. Both the hormone-mediated increase in cell GSH and GCS activity were blocked with either cycloheximide or actinomycin D. Finally, when studied in vivo, streptozotocin-treated diabetic and adrenalectomized rats exhibited lower hepatic GSH levels and GCS activities than respective controls. Both of these abnormalities were prevented with hormone replacement. Thus, both in vitro and in vivo, In and glucocorticoids are required for normal expression of GCS.
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PMID:Insulin and glucocorticoid dependence of hepatic gamma-glutamylcysteine synthetase and glutathione synthesis in the rat. Studies in cultured hepatocytes and in vivo. 135 65

Fulminant hepatitis shows characteristic imbalance of amino acid levels; increased aromatic amino acid (AAA) and methionine. Elevated plasma AAA may cause hepatic encephalopathy and BCAA-enriched amino acids solution (BCAAs). Glucagon-Insulin (G-I) therapy and artificial liver support system have been proposed to correct the imbalance of amino acids. BCAAs and G-I therapy correct the aberrant amino acid patterns and artificial liver support system, including plasma pheresis, and charcoal haemoperfusion has also been used to reduce plasma amino acids levels. While imbalance of amino acids level in fulminant hepatitis is a result of acute necrosis of a large proportion of hepatocytes, careful and sufficient management of the disease is essential to normalize amino acid profiles.
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PMID:[Imbalance of amino acid metabolism in fulminant hepatitis and its management]. 140 90

A growth hormone-releasing factor (GRF)-like peptide was isolated from the hypothalamus of common carp, Cyprinus carpio, by acid extraction, gel filtration chromatography, immunoaffinity chromatography using antiserum directed against rat GRF, and multiple steps of HPLC using octadecyl columns. Based on Edman degradation and peptide mapping, this teleost GRF was established to be a 45-residue peptide with the following primary structure: His-Ala-Asp-Gly-Met-Phe-Asn-Lys-Ala-Tyr-Arg-Lys-Ala-Leu-Gly-Gln-Leu-Ser- Ala-Arg - Lys-Tyr-Leu-His-Thr-Leu-Met-Ala-Lys-Arg-Val-Gly-Gly-Gly-Ser-Met-Ile-Glu- Asp-Asp-Asn-Glu-Pro-Leu-Ser. Carp GRF is closely related structurally to peptides of the glucagon-secretin superfamily, and more particularly to mammalian vasoactive intestinal peptide (VIP) precursors and the N-terminal portion of mammalian GRFs. A synthetic replicate of this peptide is highly potent [50% effective dose (ED50) approximately 0.08 nM] in stimulating GH release from cultured goldfish pituitary glands and in elevating serum GH levels 30 min after injection (0.1 micrograms/g) in goldfish.
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PMID:Isolation and characterization of hypothalamic growth-hormone releasing factor from common carp, Cyprinus carpio. 147 12

The basic therapeutic principle in alcoholic liver diseases in general and in alcoholic hepatitis in particular is the consequent withdrawal of alcohol intake. Basic therapy of more complicated causes includes well balanced nutrition and symptomatic treatment according to the known principles of hepatology and intensive care medicine. Infusions with glucose-glucagon-insulin, or the administration of silymarin, and in individual cases of glucocorticoids seems to be justified as additional treatment. The therapy with S-adenosyl-L-methionine is promising, but clear evidence of the therapeutic effect has to be supplied by clinical studies. Liver transplantation should be taken into consideration in prognostically infaust cases.
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PMID:[Therapy of alcoholic hepatitis]. 160 97

Leucine has been reported to be an important regulator of protein metabolism. We investigated the effect of intravenous infusion of L-leucine versus saline on amino acid metabolism in eight healthy human subjects. Plasma concentrations of amino acids were measured and protein turnover was estimated using L-(1-13C)lysine and L-(3,3,3,-2H3)leucine as tracers. Glucose kinetics were measured using D-(6,6-2H2)glucose as a tracer. Leucine infusion increased the plasma leucine concentration from 103 +/- 8 to 377 +/- 35 mumol/L (P less than .01). Plasma concentrations of essential amino acids, including threonine, methionine, isoleucine, valine, tyrosine, and phenylalanine were significantly decreased by leucine infusion. Leucine infusion did not change lysine flux significantly (108 +/- 4 during saline v 101 +/- 4 mumol/kg/h-1 during leucine infusion), but decreased lysine oxidation (13.2 +/- 0.9 v 10.7 +/- 1 mumol/kg/h, P less than .05) and endogenous leucine flux (from 128 +/- 4 to 113 +/- 7 mumol/kg/h, P less than .05) when plasma (2H3) ketoisocaproate (KIC) was used for calculation. During leucine infusion, the (2H3) KIC to (2H3) leucine plasma enrichment ratio increased from 0.76 +/- 0.02 to 0.88 +/- 0.01 (P less than .001), while estimation of leucine flux using plasma (2H3) leucine showed no change in endogenous leucine flux. Leucine infusion decreased hepatic glucose production and metabolic clearance of glucose, but did not change plasma concentrations of glucose, insulin, C-peptide, glucagon, epinephrine, norepinephrine, or free fatty acids. We conclude that leucine spares glucose and lysine catabolism and decreases plasma concentrations of essential amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of leucine on amino acid and glucose metabolism in humans. 164 Aug 50

1. Localization and pharmacological properties of the vasoactive intestinal polypeptide (VIP) receptors in rat circle of Willis arteries and in the arteries of pial-arachnoid membrane were studied using light microscope autoradiography combined with radioreceptor binding techniques. 2. [125I]-VIP was specifically bound to sections of rat cerebral arteries with a dissociation constant value of 0.5 nM and a binding site density of 80 fmol mg protein-1. Radioreceptor binding experiments revealed that the binding characteristics of [125I]-VIP were consistent with the labelling of specific VIP receptors. The rank order of potency of various substances tested to inhibit [125I]-VIP binding was the following: VIP greater than peptide histidine methionine greater than secretin greater than glucagon. 3. Light microscope autoradiography revealed the localization of [125I]-VIP binding sites in the medial layer of circle of Willis and pial arteries. Quantitative determination of [125I]-VIP binding site density in the different circle of Willis arteries demonstrated a higher accumulation of silver grains in the anterior than in the posterior cerebral arteries. Pial arteries are richer in VIP receptor sites than circle of Willis arteries. 4. These results suggest that the physiological neurogenic vasodilation elicited by VIP on cerebral arteries is mediated by the interaction with specific receptor sites located primarily within cerebral vessels structures involved in the control of cerebrovascular resistances.
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PMID:Vasoactive intestinal polypeptide receptors in rat cerebral vessels: an autoradiographic study. 166 Aug 95

To study the effect of ammonia administration on amino acids and indoleamines in cerebrospinal fluid (CSF) and on amino acids, insulin, and glucagon in plasma in humans with liver cirrhosis, we performed seven ammonia tolerance tests on six patients with stable liver cirrhosis. The grade of encephalopathy was determined by psychometric tests. Only one of the patients had pronounced encephalopathy. The other patients had no or only slight encephalopathy. The plasma concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, and methionine decreased after the ammonia load, whereas no changes were found in the plasma concentrations of glucagon and insulin. In CSF the concentrations of glutamine, aromatic amino acids, and indoleamines increased only in the patient who had pronounced encephalopathy, whereas no changes were found in the other patients. The effect of an ammonia load on the concentrations of neutral amino acids in CSF in patients with pronounced encephalopathy remains to be demonstrated.
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PMID:The effects of ammonia tolerance tests on the cerebrospinal fluid concentrations of amino acids and indoleamines in patients with liver cirrhosis. 169 97

Cross-reaction of a rat monoclonal antibody (BTP-1) against seventeen substance P analogues was studied. The antibody was of IgG type and related to the carboxyl terminal of substance P, especially methionyl in the terminal, but did not depend on the strength of antagonistic effects of these analogues. It did not show cross-reaction with the following nine peptides: glucagon, endorphin, angiotensin I, II, leucine-enkephalin, methionine-enkephalin, bradykinin, oxytocin and dernorthin, indicating its high specificity to substance P. By means of immuno-enzyme histochemical method, it was shown that stained nerve fibers were located in the gelaliternous substance of Rolando, interpeduncular nucleus, substantia nigra and nerve cell bodies in the vestibular nucleus, lateral tegmental nucleus of mesencephalon and ventral region of third ventricle.
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PMID:[Study of characteristics of monoclonal antibody against substance P]. 169 64

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

Vasoactive intestinal polypeptide (VIP) is a gut neuroendocrine polypeptide that increases cyclic adenosine monophosphate (cAMP) production in cells with VIP receptors. Some gastrointestinal cancer cells possess functional receptors for VIP; however, the role of VIP in regulation of growth of gastric cancer cells has not been determined. The purpose of this study was to determine whether VIP and other agents that increase cAMP regulate growth of a human gastric cancer cell line (AGS) and whether these agents regulate expression of c-myc proto-oncogene, which is required for cell proliferation. We measured levels of cAMP by radioimmunoassay, and we used Northern blot analysis to examine c-myc messenger RNA expression. Cell-growth studies were carried out in media supplemented with 3% serum, and cells were counted with a Coulter counter. We found that VIP significantly increased cAMP production of AGS cells in a dose-dependent manner, whereas secretin, glucagon, and peptide histidine methionine (PHM) did not stimulate cAMP production. Exogenous cAMP (8-bromo-cAMP) inhibited AGS cell growth in a dose-dependent manner. VIP acted synergistically with either isobutylmethyl-xanthine or forskolin to inhibit AGS cell proliferation. The increased c-myc expression, which was induced by serum, was inhibited by simultaneous treatment with VIP and isobutylmethyl-xanthine. We have found that AGS cells have specific, functional VIP receptors (activation of which are negatively correlated with cell growth) and that the mechanism by which VIP acts to inhibit cell growth appears to be due, in part, to cAMP-dependent regulation of c-myc proto-oncogene expression.
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PMID:Vasoactive intestinal polypeptide inhibits c-myc expression and growth of human gastric carcinoma cells. 171 57


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