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)

Basic and stimulated intracellular cAMP concentrations were measured in normal chicken liver and MC-29-virus-derived transplantable hepatoma (VTH) slices after in vitro incubation. Data indicated the preservation of catecholamine receptor but a loss of glucagon receptor in VTH. Comparing the relative stimulatory action of various catecholamines on cAMP concentration it was concluded that as in normal liver a predominantly beta 2-adrenergic receptor exists in the VTH, but its response to adrenaline is greater. Vinca alkaloids induced higher cAMP concentration in VTH than in normal liver. This stimulation was abolished by glucagon, while catecholamines and Vincristine acted in a synergistic manner on cAMP concentration.
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PMID:Further studies on the biochemical characterization of the MC-29 virus derived transplantable hepatoma (VTH). II. Modification of cyclic adenosine-3',5'-monophosphate levels by catecholamines, glucagon and Vinca alkaloids in normal chicken liver and VTH. 609 66

The hepatic glucagon receptor was covalently labeled with [125I-Tyr10]-monoiodoglucagon by use of the heterobifunctional crosslinker hydroxysuccinimidyl-p-azidobenzoate and analyzed by SDS-gel electrophoresis. The autoradiogram of the gel showed one band at Mr = 63,000 that was sensitive to excess unlabeled glucagon and GTP. The labeled receptor was solubilized with Lubrol-PX and the hydrodynamic characteristics of the receptor were determined. The molecular parameters of the solubilized receptor are S20,w = 4.3 +/- 0.1, Stokes radius = 6.3 +/- 0.1 nm, frictional coefficient f/f degrees = 1.8 and a calculated Mr = 119,000. Incubation of liver membranes at 32 degrees for 15 min prior to the addition of [125I-Tyr10] permitted us to identify the high molecular weight form (Mr approximately equal to 113,000) by direct SDS-gel electrophoretic analysis. Limited elastase treatment of the hormone-occupied receptor results in the appearance of a Mr = 33,000 fragment, that retains guanine nucleotide sensitivity. Elastase treatment of vacant receptors results in a Mr = 24,000 fragment that binds hormone in a GTP-sensitive manner. The Mr = 24,000 fragment is contained within the Mr = 33,000 fragment. The Mr = 63,000 receptor upon treatment with endo-beta-N-acetylglucosamine F for 4 h yields four fragments of apparent Mr = 61,000, 56,000, 51,000, and 45,000; 24 h treatment results in the accumulation of the last two fragments. Neither Mr = 33,000 and 24,000 fragment appear to be substrates for endo-beta-N-acetylglucosaminidase F. These data allow us to conclude that the hepatic glucagon receptor in the membrane is a dimer of approximately 60,000 dalton hormone binding subunit which is a glycoprotein containing at least four N-linked glycans accounting for 18,000 daltons of its mass. Both the hormone binding function and the capacity for the interaction with the stimulatory regulator of adenylyl cyclase are contained within a fragment of only approximately 21,000 daltons that does not contain any N-linked glycans.
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PMID:Characterization of the hepatic glucagon receptor. 609 55

Serum insulin and glucagon levels and liver plasma membrane receptor binding were studied in rats after partial hepatectomy. To clarify whether the surgical stress and decreased food intake that accompanies partial hepatectomy influenced these parameters, sham-operated rats were also studied. When sham-operated rats were compared to nonoperated controls, there was a 30% fall in insulin levels and a significant rise in the number of insulin receptors. In contrast, glucagon levels and glucagon receptor binding were unchanged. When partially hepatectomized rats were compared to sham-operated rats, there was no significant change in either insulin levels or the number of plasma membrane insulin receptors. Insulin degradative activity, however, was decreased in liver plasma membranes from partially hepatectomized animals, causing an apparent increase in [125I]iodoinsulin binding to this organelle. Bacitracin, an inhibitor of insulin degradation, abolished this difference in insulin binding. Glucagon levels rose by 65% after partial hepatectomy, whereas the number of glucagon receptors decreased significantly. The studies demonstrate, therefore, that after partial hepatectomy, serum insulin levels and insulin receptor binding in liver are altered, and these alterations are due to surgical stress and decreased food intake. Glucagon levels and glucagon receptor binding are also altered after partial hepatectomy, but these alterations are due to liver regeneration per se.
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PMID:Regenerating rat liver: insulin and glucagon serum levels and receptor binding. 626 53

The photoaffinity crosslinker hydroxysuccinimidyl-p-azidobenzoate was used to attach (125)I-labeled glucagon covalently to a rat liver membrane protein of M(r) approximately 53,000. Membranes that had been incubated with (125)I-labeled glucagon were treated in the dark with hydroxysuccinimidyl-p-azidobenzoate, and a covalent complex was then formed by irradiation with ultraviolet light. Characteristics of (125)I-labeled glucagon binding and covalent attachment to the M(r) 53,000 peptide were consistent with this peptide being a component of the glucagon receptor involved in the activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. Binding and covalent attachment of (125)I-labeled glucagon to the M(r) 53,000 peptide were inhibited by glucagon concentrations that were within the dose-response curve for adenylate cyclase activation, and GTP specifically decreased the photoaffinity crosslinking of (125)I-labeled glucagon to the M(r) 53,000 peptides. Insulin did not compete for the photoaffinity crosslinking of (125)I-labeled glucagon. The same technique of photoaffinity crosslinking that covalently attached (125)I-labeled glucagon to the M(r) 53,000 peptide with an efficiency of 1-2% can be used to attach (125)I-labeled insulin covalently to a M(r) 125,000 peptide with an efficiency of approximately 10%. This peptide has been shown to be a subunit of the high-affinity insulin-binding site in rat liver membranes. The technique of photoaffinity crosslinking with agents like hydroxysuccinimidyl-p-azidobenzoate provides a rapid, simple method of covalently attaching ligands to their putative receptors. Photoaffinity crosslinking does not require chemical modification of the labeled ligand and has a less stringent requirement for specific reactive groups than the commonly used bifunctional crosslinking reagents.
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PMID:Identification of the glucagon receptor in rat liver membranes by photoaffinity crosslinking. 626 79

Spontaneously transformed RL-PR-C rat hepatocytes, unlike their normal differentiated progenitor cells, are insensitive to glucagon, although seemingly possessing large numbers of glucagon receptors and although retaining guanyl nucleotide regulatory protein-adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] system that responds to catecholamines, cholera toxin, and fluoride ions. Biochemical fusions between normal RL-PR-C hepatocytes or purified rat liver plasma membranes (whose adenylate cyclases were previously irreversibly inactivated with N-ethylmaleimide) with spontaneously transformed hepatocytes produced hybrids whose basal and fluoride-stimulated adenylate cyclase activities reflected those of the parental transformed cells but that now responded to glucagon. Using cholera toxin-catalyzed ADP-riboxylation of transformed hepatocytes to mark their guanyl nucleotide regulatory protein, fusiong such cells with N-ethylmaleimide-treated normal hepatocytes, and examining glucagon stimulation of adenylate cyclase activity in fusion hybrids produced results suggesting that the regulatory protein of the transformed cells is functionally normal. In fusion experiments between N-ethylmaleimide-treated hepatocytes and igeon erythrocytes, we found that normal, but not transformed, hepatocytes were effective in conferring glucagon sensitivity upon erythrocytes. Glucagon binding data revealed that, whereas normal RL-PR-C hepatocytes have two independent classes of binding sites, one of higher and the other of lower affinity, transformed cells possess only the low-affinity receptors. From these and previous observations, it is possible to conclude that the insensitivity of spontaneously transformed RL-PR-C hepatocytes to glucagon is due to the loss, during the transformation process, of the high-affinity glucagon receptor.
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PMID:Restoration of glucagon responsiveness in spontaneously transformed rat hepatocytes (RL-PR-C) by fusion with normal progenitor cells and rat liver plasma membranes. 626 32

A series of glucagon analogues, des-(1-4)-glucagon, des-(5-9)-glucagon, des-(10-15)-glucagon, des-(16-21)-glucagon, des-(22-26)-glucagon and des-(27-29)-glucagon, were prepared by condensation of synthetic fragments and characterized biologically and immunologically. Fully synthetic glucagon was also characterized. The potencies with regard to glucagon receptor binding in purified rat liver plasma membranes were, in decreasing order: synthetic glucagon 108%, des-(1-4)-glucagon 5.7%, des-(27-29)-glucagon 0.92%, des-(5-9)-glucagon 0.47%, des-(10-15)-glucagon 0.0028%, des-(16-21)-glucagon 0.0017% and des-(22-26)-glucagon 0.00060% relative to that of natural porcine glucagon. Des-(27-29)-glucagon was the only analogue that activated the adenylate cyclase in rat liver plasma membranes or stimulated the lipolysis in isolated free fat cells from rat epididymal fat pad. The potencies were 0.16% and 0.20% of that of glucagon, respectively. Des-(1-4)-glucagon was a glucagon antagonist in the adenylate cyclase assay. The immunoreactivities of the glucagon analogues were determined with two commonly used anti-glucagon sera, K 5563 and K 4023, directed towards the C-terminus and some segment in the sequence 2-23, respectively. In the K 5563 assay, des-(27-29)-glucagon and des-(22-26)-glucagon had potencies of 0.0009% and less than 0.09% of that of glucagon, respectively. The remaining analogues had potencies varying from 45% to 141% of that of glucagon. In the K 4023 assay, the analogues showed a non-linear dilution effect. The combined results indicate a partition within the glucagon molecule with regard to receptor binding and adenylate cyclase activation. The region 10-26 appears to be the most important for receptor binding, whereas 1-4 is essential for adenylate cyclase activation. The C-terminal segment 27-29 is important for the maintenance of full receptor binding but non-essential for adenylate cyclase activation.
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PMID:Glucagon: structure-function relationships investigated by sequence deletions. 626 19

Insulin and glucagon receptors were measured on hepatocytes in relation to circulating hormones (insulin, glucagon and growth hormone) and metabolites (non-esterified fatty acids, volatile fatty acids, glucose, total lipids, urea and alpha-amino nitrogen), in twelve, two-year old, castrated male goats, fed rations of different composition and dietary energy. The goats were separated into four groups; group 1 was fed a restricted ration of 600 g clover hay/day, group 2 a ration high in carbohydrate (rolled barley), group 3 a ration high in fat (protected tallow) and group 4 a ration high in protein (fish meal). Rations in groups 2 - 4 were fed at 1300 g/day supplemented with 600 g of clover hay. The binding of insulin to hepatocyte receptors was increased by restricting dietary intake when compared to the high energy intake groups (p less than 0.01). There was no significant difference between the insulin binding of groups 2 -4. Glucagon receptor binding was increased on the high protein diet in comparison with th ration high in carbohydrate (p less than 0.05) or in fat (p less than 0.01). The glucagon binding was reduced by restricting feed intake when compared wih feeding high protein (p less than 0.02), but slightly increased when compared with feeding diets high in both carbohydrate or fat (p less than 0.02). There was no significant difference between the high carbohydrate or high fat fed groups. These changes in hormone receptors were accompanied by inverse changes in plasma insulin and glucagon.
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PMID:Insulin and glucagon binding to hepatocytes in relation to circulating hormones and metabolites in goats maintained on different diets. 627 75

A subject with a benign glucagonoma was studied before and after complete resection of his pancreatic tumour. Studies were undertaken pre- and post-operatively to determine the effects of chronic hyperglucagonaemia on glucose tolerance and glucose kinetics both in the fasting state and during physiological insulin infusions, employing the [3H]-3-glucose technique. In addition the plasma cyclic AMP response to an acute infusion of glucagon was studied pre- and post-operatively. The basal immunoreactive glucagon levels pre- and post-operatively were 10492 +/- 1296 and 149 +/- 15 pg/ml respectively. Pre- and post-operative oral glucose tolerance tests did not differ but were abnormal. Pre-operatively basal hepatic glucose production was normal and it was suppressed rapidly by the low dose insulin infusion, despite continuing hyperglucagonaemia. The metabolic clearance rate of glucose was slightly reduced. There was no plasma cyclic AMP response to a glucagon infusion, suggesting down-regulation of the glucagon receptor by the chronic hyperglucagonaemia. Post-operatively the hepatic glucose production and clearance rate of glucose fell, whereas the plasma cyclic AMP responses to the glucagon infusion reverted to a normal pattern. It is concluded that chronic hyperglucagonaemia is not a major factor in the development of the glucose intolerance, but it may lead to down-regulation of the biological action of glucagon.
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PMID:The metabolic effects of chronic hyperglucagonaemia. 627 44

The ability of 10 muM epinephrine or isoproterenol to stimulate cyclic AMP accumulation was decreased in hepatocytes isolated from hyperthyroid (triiodothyronine treated) as compared to euthyroid rats. In the presence of methylisobutylxanthine, epinephrine or isoproterenol-stimulated cyclic AMP accumulation was approximately 65% lower in hyperthyroid as compared with euthyroid rat hepatocytes. The ability of glucagon to stimulate a cyclic AMP response was also decreased in the hyperthyroid state, when assayed in either the absence or presence of a methyl xanthine. The character of the catecholamine-stimulated cyclic AMP response was beta adrenergic in both the hyperand euthyroid states. No evidence for an alpha(2) adrenergic mediated component of catecholamine action on cyclic AMP levels was noted. Cyclic AMP phosphodiesterase activity of hepatocyte homogenates was not altered in the hyperthyroid state. Hormone-stimulated, guanine nucleotide- and fluoride-activatable adenylate cyclase activity was reduced in subcellular fractions obtained from hyperthyroid as compared with euthyroid rat hepatocytes. Beta adrenergic receptor binding was reduced approximately 35% and glucagon receptor binding reduced approximately 50% in the hyperthyroid as compared with euthyroid rat hepatocyte membrane fractions. The status of the regulatory components of adenylate cyclase were examined by in vitro treatment of subcellular fractions with cholera toxin. The ability of cholera toxin to modulate adenylate cyclase was not altered by hyperthyroidism. Cholera toxin catalyzed AD[(32)P]ribosylation of hyperthyroid and euthyroid rat hepatocyte proteins separated electrophoretically displayed nearly identical autoradiograms. Studies of the reconstitution of adenylate cyclase activity of S49 mouse lymphoma cyc(-) mutant membranes by detergent extracts from rat hepatocyte membranes, indicated that hyperthyroidism was associated with a reduced capacity of regulatory components to confer fluoride, but not guanine nucleotide activatability to catalytic cyclase. Thyroid hormones regulate the hormone-sensitive adenylate cyclase system of rat hepatocytes at several distinct loci of the system.
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PMID:3,3',5-triiodothyronine administration in vivo modulates the hormone-sensitive adenylate cyclase system of rat hepatocytes. 627 41

Insulin and glucagon secretion after glucose load and the hormone-receptor inter-action were compared between 6- and 24-month-old Wistar rats. The 24-month-old rats showed a failure to decrease glucagon secretion after glucose load in contrast to 6-month-old rats with a similar degree of glucose tolerance and insulin response. Age-related change of insulin receptor of rat livers was tentatively suggested to be a disappearance of the binding site with higher affinity. Affinity of the glucagon receptor did not differ significantly between the two groups. The hyposuppressibility of glucagon by hyperglycemia and the decrease of insulin affinity might contribute to the glucose intolerance with aging.
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PMID:Insulin insensitivity and hyposuppressibility of glucagon by hyperglycemia in aged Wistar rats. 627 41


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