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)

A radioimmunoassay procedure for guanosine 3',5'-cyclic monophosphate (CGMP) is described. The procedure is based on competitive binding between [3H]CGMP and non-radioactive CGMP, with separation of bound and unbound CGMP by Millipore filtration. The binding reaction showed very high specificity to CGMP, had a broad pH optimum, and reached equilibrium within a short time. A simple procedure for the pruification of assay samples using Dowex AG 50W-X2 resin is also described. CGMP contents in urine samples were assayed without purification. Injection of glucagon into healthy human volunteers resulted in a small but significant reduction in urinary CGMP level, whereas CAMP excretion increased dramatically.
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PMID:Rapid radioimmunoassay for guanosine 3',5'-cyclic monophosphate using tritiated ligand. 0 Mar 74

In immunohistochemical studies of rat liver tissue slices and purified nuclei, adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) immunofluorescence on the nuclear membrane are sequentially increased after glucagon administration. An explanation for the increased cGMP immunofluorescence was sought in experiments in which guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2]activity of hepatic subcellular fractions was determined. The results showed that a nuclear guanylate cyclase exists which can be distinguished from the soluble and crude particulate guanylate cyclases. The activity of the nuclear enzyme was increased by 35% in nuclei isolated from rats 30 min after glucagon injection, the time at which maximal nuclear membrane cGMP immunofluorescence is observed. Because glucagon altered both cAMP location and levels prior to the observed changes in nuclear cGMP metabolism, the hypothesis that cAMP acted as the second messenger was tested. In vitro incubation of nuclei isolated from control rats with 10(-5) M cAMP produced a 25% increase in nuclear guanylate cyclase activity. With nuclei isolated from glucagon-treated rats, no significant increase in enzyme activity was observed; this indicates that maximal stimulation of nuclear guanylate cyclase by cAMP occurred at levels that are obtained in vivo after glucagon administration. These findings suggest that hepatic nuclear cGMP content may be regulated by a specific organelle guanylate cyclase and that cAMP may be one of the determinants of this enzyme's activity.
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PMID:Regulation of hepatic nuclear guanylate cyclase. 1 62

The examination of the regulation of the system of 3'-5' cyclic nucleotide monophosphates has only begun in cancer tissues. In human cancers, these studies are notably non-existent. However, in animal cancers, especially the Morris hepatomas, enough data has been gathered that, while risky, certain trends seem to begin to appear. Cyclic AMP is constant or lowered, while cyclic GMP is elevated in the fast growing hepatomas. Regulation of adenylate cyclase by protein hormones is reduced, while regulation by epinephrine may be increased. Binding of glucagon is decreased in the fast growing hepatomas. Guanylate cyclase, while being predominantly cytoplasmic in the normal liver, is predominantly membrane bound in the tumors. The liver enzyme is also readily stimulated by several chemical carcinogens. The cyclic GMP phosphodiesterases are decreased in these tumors; while the cAMP phosphodiesterases are increased. Although the cyclic nucleotide dependent protein kinases (histone as substrate) are altered in the hepatomas, observations of unique cyclic nucleotide binding proteins or cAMP independent protein kinases in cancer tissues may be of even greater significance for the development of or the maintenance of the neoplastic state of cells.
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PMID:Cyclic nucleotide metabolism in solid tumor tissues. 2 89

Gluconeogenesis from lactate, pyruvate, fructose, alanine, and other substrates was accelerated by glucagon or epinephrine in hepatocytes isolated from rat liver. Glucagon and epinephrine also increased cyclic AMP accumulation by rat hepatocytes. Isoproterenol increased cyclic AMP but not gluconeogenesis, while phenylephrine accelerated gluconeogenesis. The activation of gluconeogenesis by epinephrine was unaffected by propranolol but blocked by dihydroergotamine. Dibutyryl cyclic AMP added to hepatocytes stimulated gluconeogenesis at concentrations as low as 1 muM. Exogenous cyclic GMP (0.1- muM) inhibited gluconeogenesis due to either glucagon or epinephrine without affecting basal gluconeogenesis. However, carbamylcholine did not affect gluconeogenesis by hepatocytes. Basal gluconeogenesis and the increases due to all agents were inhibited by removal of extracellular calcium or the presence of A-23187, D-600, or tetracaine. In contrast, added 0.1 muM cyclic GMP, 2 mM NH-4-Cl, and 10 muM phenethylbiguanide inhibited glucagon- or epinephrine-stimulated gluconeogenesis without affecting basal values. Studies with hepatocytes indicate that the hormonal activation of gluconeogenesis is not limited to substrates entering prior to triose phosphate formation. Glucagon may act by increasing cyclic AMP which acts via unknown mechanisms to increase gluconeogenesis. In contrast, epinephrine acts via a cyclic AMP-independent mechamism which does not appear to involve cyclic GMP, Ca-2+ flux, of K+ flux.
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PMID:Cyclic nucleotides and gluconeogenesis by rat liver cells. 16 60

Insulin action is discussed with emphasis on events that occur at the plasma membrane. A summary is presented of previous studies which indicate that the insulin receptor of fat and liver cells is a large glycoprotein, partially buried in the outer surface of the plasma membrane, with a high (K-D approximately 10-10 M) and specific affinity for insulin. The participation of membrane phospholipids in the binding of insulin and the role of sialic acid residues in the transmission of the insulin binding signal are discussed. The relation of insulin action to its effects on cyclic nucleotide levels is explored. On the one hand, insulin action (glucose transport) is inhibited by compounds (cholera toxin, ACTH, glucagon and L-norepinephrine) that stimulate adenylate cyclase; conversely, insulin both inhibits the lipolytic action of these compounds, and raises cellular levels of cyclic GMP. An hypothesis is presented whereby a single cyclase species may be responsible for the formation of either cyclic AMP or cyclic GMP, depending on the nature of the hormone stimulus. The role of membrane phosphorylation in the action of insulin is discussed in the context of experiments demonstrating a specific inhibition by ATP of insulin-mediated glucose transport, in association with the phosphorylation of two specific membrane proteins. The ability of insulin to modulate cyclic nucleotide levels in cultured cells and to act as a growth factor is discussed. Insulin stimulates DNA synthesis and the uptake of alpha-aminoisobutyric acid in human fibroblasts, which effects are also mediated by epidermal growth factor. Insulin acts at concentrations much higher than those obtained in vivo, whereas epidermal growth factor acts at concentrations thought to be physiological. The insulin binding sites (K-D is approximately equal to 10-9 M) related to growth, and observed both in human fibroblasts and in lectin-stimulated and leukemic human lymphocytes would not be appreciably occupied at physiological insulin concentrations. The implications of such 'low affinity' binding sites for insulin are discussed in relation to the action of other growth factors.
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PMID:Insulin: interaction with membrane receprots and relationship to cyclic purine nucleotides and cell growth. 16 82

Cyclic GMP and cyclic AMP have been localized in rat liver, small intestine, and testis by a fluorescent immunocytochemical procedure. In liver, cyclic AMP is distributed along sinusoids predominantly, and increased fluorescence is seen sinusoidal areas after glucagon administration. Cyclic GMP is located in nuclear elements and on the plasma membranes of hepatocytes. In jejunum, cyclic AMP is found predominantly at the basal and lateral sides of brush border cells and in the lamina propria, while cyclic GMP is located to the brush border membrane, smooth muscle, and nuclear elements. In testis, cyclic AMP is found in cytoplasm of cells at the perimeter of the seminiferrous tubules and in interstitial cells, while cyclic AMP is visualized on the plasma membrane of the cells lining the tubules. Cyclic GMP is also seen on chromosomes of premeiotic spermatocytes and in sperm. These data provide histological evidence implicating diverse roles for the nucleotides in these tissues. The nuclear localization of cyclic GMP in all of these tissues suggests a role for the nucleotide in nucleus-directed events.
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PMID:Immunohistochemical localization of 3': 5'-cyclic AMP and 3': 5'-cyclic GMP in rat liver, intestine, and testis. 16 76

Isolated rat hearts were perfused with hormonal concentrations of glucagon during a hypoxic perfusion to determine whether it would enhance recovery after reoxygenation. Rat hearts were divided into two groups: (1) those perfused with glucose-free Tyrode's solution and (2) those perfused with Tyrode's solution containing glucose. During 3 minutes of exposure to hypoxia both untreated hearts and hearts perfused with glucagon demonstrated a decrease in contractile force to 10-20% of control. When glucose was present in the perfusion medium, cardiac performance was better during both the periods of hypoxia and reoxygenation. During reoxygenation, recovery of contractile force was significantly better (P less than 0.05) in glucagon-perfused hearts than in untreated hearts; this improved recovery occurred regardless of whether glucose was included in the medium. The enhanced recovery of the glucagon-perfused hearts was associated with decreases in myocardial levels of guanosine, 3',5'-monophosphate (cyclic GMP) both during the periods of hypoxia and reoxygenation. At the end of the hypoxic period, cyclic GMP levels in the glucagon-perfused hearts were 20-64% of the levels in untreated hearts. Similarly, after 5 minutes of reoxygenation cyclic GMP levels in the glucagon-perfused hearts were 21% of the levels in the untreated hearts. The effect of glucagon on adenosine 3',5'-monophosphate (cyclic AMP) concentrations in untreated hearts and in hearts receiving glucagon was not significantly different either after 3 minutes of hypoxia or during reoxygenation. The rate of anaerobic glycolysis after 3 minutes of hypoxia was higher in untreated hearts than in glucagon-perfused hearts, as determined by the lactate content of coronary perfusates. These studies suggest that hormonal concentrations of glucagon exert a protective effect on the hypoxic rat heart which involves a modulation of cardiac cyclic GMP accumulation.
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PMID:Changes in cyclic nucleotide levels and contractile force in the isolated hypoxic rat heart during perfusion with glucagon. 17 33

Insulin (10nM) completely suppressed the stimulation of gluconeogenesis from 2 mM lactate by low concentrations of glucagon (less than or equal to 0.1 nM) or cyclic AMP (less than or equal to 10 muM), but it had no effect on the basal rate of gluconeogenesis in hepatocyctes from fed rats. The effectiveness of insulin diminished as the concentration of these agonists increased, but insulin was able to suppress by 40% the stimulation by a maximally effective concentration of epinephrine (1 muM). The response to glucagon, epinephrine, or insulin was not dependent upon protein synthesis as cycloheximide did not alter their effects. Insulin also suppressed the stimulation by isoproterenol of cyclic GMP. These data are the first demonstration of insulin antagonism to the stimulation of gluconeogenesis by catecholamines. Insulin reduced cyclic AMP levels which had been elevated by low concentrations of glucagon or by 1 muM epinephrine. This supports the hypothesis that the action of insulin to inhibit gluconeogenesis is mediated by the lowering of cyclic AMP levels. However, evidence is presented which indicates that insulin is able to suppress the stimulation of gluconeogenesis by glucagon or epinephrine under conditions where either the agonists or insulin had no measurable effect on cyclic AMP levels. Insulin reduced the glucagon stimulation of gluconeogenesis whether or not extracellular Ca2+ were present, even though insulin only lowered cyclic AMP levels in their presence. Insulin also reduced the stimulation by epinephrine plus propranolol where no significant changes in cyclic AMP were observed without or with insulin. In addition, insulin suppressed gluconeogenesis in cells that had been preincubated with epinephrine for 20 min, even though the cyclic AMP levels had returned to near basal values and were unaffected by insulin. Thus insulin may not need to lower cyclic AMP levels in order to suppress gluconeogenesis.
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PMID:Regulation by insulin of gluconeogenesis in isolated rat hepatocytes. 17 43

Isolated rat hearts were perfused with a subinotropic concentration of glucagon during an hypoxic perfusion to determine whether glucagon would enhance recovery upon reoxygenation. Rat hearts were divided into two groups: 1) those perfused with glucose-free Tyrode's solution and 2) those perfused with Tyrode's solution containing glucose. During 3 min of hypoxic exposure, untreated hearts and hearts perfused with glucagon both demonstrated a dramatic decrease in contractile force regardless of whether glucose was included in the medium. However, when glucose was present in the perfusion medium cardiac performance was better during both hypoxia and the period of reoxygenation. Furthermore, during reoxygenation, the recovery of contractile force was significantly greater in glucagon-perfused hearts than in controls. Cardiac levels of cyclic AMP and cyclic GMP were monitored at various periods of hypoxic exposure to test the existence of a correlation between the concentrations of these cyclic nucleotides and cardiac performance. During reoxygenation of untreated hearts, the hearts perfused with glucose-free medium attained 45-50 percent of the contractile force seen in glucagon-treated hearts. This enhanced recovery in the glucagon-treated hearts was associated with decreases in cyclic GMP levels at the end of the hypoxic period. At this time, the cyclic GMP levels in the glucagon-treated hearts were only 25-55 percent of the levels seen in untreated hearts that were also exposed to hypoxia. The effect of glucagon on cyclic AMP content in untreated hearts and in hearts receiving glucagon was not significantly different at 3 min of hypoxia. These studies suggest that subinotropic concentrations of glucagon exert a protective effect on the hypoxic rat heart that is not related to the direct inotropic properties of this hormone but which may involve a modulation in cardiac cyclic GMP availability.
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PMID:Effects of glucagon on cardiac cyclic nucleotides in the hypoxic heart. 17 99

Catecholamines increased guanosine 3':5'-monophosphate (cyclic GMP) accumulation by isolated rat liver cells. The increases in cyclic GMP due to 1.5 muM epinephrine, isoproterenol, or phenylephrine were blocked by phenoxybenzamine but not by propranolol. The possibility that cyclic GMP is involved in the glycogenolytic action of catecholamines seems unlikely since cyclic GMP accumulation is also elevated by carbachol, insulin, A23187, and to a lesser extent by glucagon. Furthermore, carbachol had little effect on glycogenolysis while insulin actually inhibited hepatic glycogenolysis. The rise in cyclic GMP due to carbachol was abolished by atropine and that due to all agents was markedly reduced by the omission of extracellular calcium. However, the glycogenolytic action of glucagon and catecholamines was only slightly inhibited by the omission of calcium. The only agent which was unable to stimulate glycogenolysis in calcium-free buffer was the divalent cation ionophore A23187. There was a drop in ATP content of liver cells during incubation in calcium-free buffer which was accompanied by an inhibition of glucagon-activated adenosine 3':5'-monophosphate (cyclic AMP) accumulation. The presence of calcium inhibited the rise in adenylate cyclase activity of lysed rat liver cells due to glucagon or isoproterenol but not that due to fluoride. These results suggest that the stimulation by catecholamines and glucagon of glycogenolysis is not mediated through cyclic GMP nor does it depend on the presence of extracellular calcium. Cyclic GMP accumulation was increased in liver cells by agents which either inhibit, have little affect, or accelerate glycogenolysis. The significance of elevations of cyclic GMP in rat liver cells remains to be established.
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PMID:Studies on the role of cyclic guanosine 3':5'-monophosphate and extracellular Ca2+ in the regulation of glycogenolysis in rat liver cells. 17 60


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