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)

The effects of the alpha-adrenergic agonist phenylephrine on the levels of adenosine 3':5'-monophosphate (cAMP) and the activity of the cAMP-dependent protein kinase in isolated rat liver parenchymal cells were studied. Cyclic AMP was very slightly (5 to 13%) increased in cells incubated with phenylephrine at a concentration (10(-5) M) which was maximally effective on glycogenolysis and gluconeogenesis. However, the increase was significant only at 5 min. Cyclic AMP levels with 10(-5) M phenylephrine measured at this time were reduced by the beta-adrenergic antagonist propranolol, but were unaffected by the alpha-blocker phenoxybenzamine, indicating that the elevation was due to weak beta activity of the agonist. When doses of glucagon, epinephrine, and phenylephrine which produced the same stimulation of glycogenolysis or gluconeogenesis were added to the same batches of cells, there were marked rises in cAMP with glucagon, minimal increases with epinephrine, and little or no changes with phenylephrine, indicating that the two catecholamine stimulated these processes largely by mechanisms not involving cAMP accumulation. DEAE-cellulose chromatography of homogenates of liver cells revealed two major peaks of cAMP-dependent protein kinase activity. These eluted at similar salt concentrations as the type I and II isozymes from rat heart. Optimal conditions for preservation of hormone effects on the activity of the enzyme in the cells were determined. High concentrations of phenylephrine (10(-5) M and 10(-4) M) produced a small increase (10 tp 16%) in the activity ratio (-cAMP/+cAMP) of the enzyme. This was abolished by propranolol, but not by phenoxybenzamine, indicating that it was due to weak beta activity of the agonist. The increase in the activity ratio of the kinase with 10(-5) M phenylephrine was much smaller than that produced by a glycogenolytically equivalent dose of glucagon. The changes in protein kinase induced by phenylephrine and the blockers and by glucagon were thus consistent with those in cAMP. Theophylline and 1-methyl-3-isobutylxanthine, which inhibit cAMP phosphodiesterase, potentiated the effects of phenylephrine on glycogenolysis and gluconeogenesis. The potentiations were blocked by phenoxybenzamine, but not by propranolol. Methylisobutylxanthine increased the levels of cAMP and enhanced the activation of protein kinase in cells incubated with phenylephrine. These effects were diminished or abolished by propanolol, but were unaffected by phenoxybenzamine. It is concluded from these data that alpha-adrenergic activation of glycogenolysis and gluconeogenesis in isolated rat liver parenchymal cells occurs by mechanisms not involving an increase in total cellular cAMP or activation of the cAMP-dependent protein kinase. The results also show that phosphodiesterase inhibitors potentiate alpha-adrenergic actions in hepatocytes mainly by a mechanism(s) not involving a rise in cAMP.
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PMID:Studies on the alpha-andrenergic activation of hepatic glucose output. II. Investigation of the roles of adenosine 3':5'-monophosphate and adenosine 3':5'-monophosphate-dependent protein kinase in the actions of phenylephrine in isolated hepatocytes. 0 57

Splenic lobes from the pancreas of newborn rats (48-64) hr. were used for the in vitro investigation of cyclic AMP, glucose and amino acid interaction in hormonal secretion. The slight discrepancy found in glucagon relaease with radioimmunoassay and binding assay to specific receptors in liver does not affect the ratio of stimulated to control values. The insulin release due to gheophylline dibutyrl cyclic AMP (dbcAMP) or to arginine is glucose-dependent as in adult rats and provides an index for the validity of the preparations. Glucose alone is efficient in stimulating insulin release but does not affect glucagon secretion; however simultaneous addition of 10 mM arginine, alanine, and lysine (A.A.) or of arginine alone resulted in a higher glucagon release at 1.6 mM than at 16.7 mM GLUCOSE. Theophylline (5 mM)and dbcAMP (2mM) induced a 2=fold increase in glucagon release at low or hight glucose concentrations . Incubation of theophylline (10 mM) and A.A. or arginine resulted in a considerable increase in glucagon release. Potentation of the 3 A.A.-induced glucagon reby dbcAMP was about 1800% no matter what the glucose concentration; similar observations were made for insulin with a 700% potentiation of the 3 A.A.effect glucagon was released more effectively by dbcAMP than was insulin,whereas the reverse was observed with theophylline. These findings suggest that knowledge of the cyclic AMP content is essential when assessing the influence of substrates on glucagon release. The combination of substrates with cyclic AMP clearly demonstrated that potentiation of glucagon release occurs mainly with amino acids, whereas for insulin occurs mainly with amino acids, whereas for insulin release it is mainly glucose which potentiates release.
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PMID:Interaction of amino acids and cyclic AMP on the release of insulin and glucagon by newborn rat pancreas. 16 77

Activation of adrenergic beta receptors has been found to stimulate insulin release in vitro that may be mediated through the augmentation of cyclic AMP in the beta cell. The activation of adrenergic alpha receptors in the beta cell inhibits the insulin release. The present studies have shown that isoproterenol (0.62 mug/ml) and sodium dibutyryl cyclic AMP (50 mug/ml) stimulate the insulin secretion and inhibit the glucagon secretion in the presence of 50 mg/100 ml glucose by the isolated pancreatic perfusion of the rat, while norepinephrine (0.5 mug/ml) inhibits the insulin secretion induced by 150 mg/100 ml glucose and stimulates the glucaton secretion. Theophylline (50 mug/ml) does not stimulate the insulin and the glucagon secretion. When norepinephrine is added to theophylline, the output of glucagon does not occur. From these results it can be deduced that the pancreatic alpha cell function may be inhibited by elevation of intracellular cyclic AMP, in contrast to the beta cell function which is stimulated by an increment of cyclic AMP.
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PMID:Secretory regulation of endocrine pancreas: Cyclic AMP and glucagon secretion. 16 30

The influence of various agents on calcitonin release from human thyroid was studied in vitro. Under the condition of this investigation, calcium, magnesium and phosphate did not stimulate calcitonin release from short-term incubated slices of human thyroid. However, pentagastrin and USP glucagon were potent stimulators of calcitonin release. Theophylline and dibutyryl cyclic AMP were also potent stimuli. A highly purified preparation of pancreatic glucagon was without an effect. Those agents which stimulated calcitonin release were associated with augmented cyclic AMP accumulation. Although maximal discharge of calcitonin required the presence of calcium, out in vitro experiments raise the question as to whether a gastrointestinal hormone, rather than calcium, might not be the principal agent affecting calcitonin release.
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PMID:In vitro studies of calcitonin release in man. 17 Dec 4

Plasma concentrations of glucose, alanine, and glucagon were measured after 24 hour fasting in newborn and infant sheep and in response to infusion of alanine alone and concurrently with theophylline. The plasma glucagon response to alanine was minimal in newborn sheep; in contrast, alanine produced a brisk response in plasma glucagon concentration in infant sheep. Glucose concentrations were unchanged in both groups. Theophylline enhanced blood glucagon and glucose responses to alanine in newborn animals but had minimal effects on the response of the infant sheep. These data, considered with earlier data in fetal sheep, suggest a progressive maturation of pancreatic islet alpha-cell glucagon secretion in the sheep during the postnatal period and suggest that the blunted glucagon response observed in the neonate is related to immaturity of the glucagon secretion mechanisms rather than deficient synthesis of the hormone. This immaturity may be related to impaired synthesis and/or enhanced degradation of cyclic adenosine monophosphate (cAMP) or to diminished responsiveness to cAMP.
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PMID:Effects of fasting and theophylline on alanine-stimulated glucagon secretion in neonatal and infant sheep. 17 57

The effect of glucagon, Vasoactive Intestinal Polypeptide (VIP), secretin and gut glucagon on the cyclic adenosine 3'5' monophosphate (cAMP) level, and on the specific binding of these 125I-peptides to the adipocyte plasma membrane was measured in chicken adipocytes and compared to the results obtained in rat adipocytes. The displacement of 125I-glucagon from its specific sites was observed with about the same concentration of unlabeled hormone in fat cell plasma membranes of both species. However, the rise in cAMP induced by glucagon was much higher in chicken than in rat adipocytes. In chicken fat cells unlike rat fat cells, the cAMP accumulation elicited by glucagon was maintained during at least 60 min even in the absence of theophylline. Theophylline at 1-10 mM potentiated the glucagon-stimulated cAMP levels in rat fat cells, but had only a slight effect, if any, in chicken adiposyces. Porcine VIP, secretin or gut glucagon exerted no detectable action on the cAMP level of chicken adipocytes. The lack of cAMP accumulation was in good agreement with the absence of binding of 125I-VIP and 125I-secretin by chicken plasma membranes. These findings suggest that: 1) the difference of glucagon effect in rat and chicken fat cells results from variations in the rate of degradation of cAMP rather than from differences in the specific binding of glucagon between the two species; 2) the use of chicken fat cells is suitable to discriminate between glucagon and structurally related peptides from mammals.
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PMID:Interactions of glucagon and related peptides with chicken adipose tissue. 18 29

The stimulatory effects of isoproterenol and secretin on external pancreatic secretion were compared in the rat. 1. In acute fistula, pylorus ligation, atropine, glucagon did not change either of the stimulated secretions. Propranolol inhibited isoproterenol-induced secretion and did not change secretin induced stimulation. Theophylline alone displayed a large hydrelatic stimulatory effect, without increasing protein excretion; the effect of theophylline was additive with the effects of isoproterenol or secretin but no evidence was found of potentiation or prolongation of action. Isoproterenol did not increase pancreatic blood flow and induced no variations in the plasma levels of immunoreactive secretin. Combining various doses of isoproterenol and secretin did not allow to reach secretory levels greater than the maximal response to secretin. 2. In conscious rats chronic fistulae, isoproterenol and secretin had a distinct effect.
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PMID:Isoproterenol induced pancreatic secretion in rats. A comparison with secretin. 19 Nov 17

In dispersed mucosal cells from guinea pig stomach cyclic AMP was increased 4-fold by theophylline, 5-fold by prostaglandin E2, and 10- to 15-fold by histamine. Theophylline augmented the increase in cellular cyclic AMP caused by histamine or prostaglandin E1 and the actions of histamine and prostaglandin E1 were additive. Cellular cyclic AMP was not altered by carbachol, gastrin, secretin, vasoactive intestinal peptide, glucagon, insulin or the octapeptide of cholecystokinin. Metiamide or diphenhydramine but not atropine inhibited the increase in cellular cyclic AMP caused by histamine, but did not alter the concentration of cyclic AMP in control cells or in cells incubated with theophylline or prostaglandin E1.
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PMID:Cellular cyclic AMP in dispersed mucosal cells from guinea pig stomach. 20 34

The effects of glucagon alone or in combination with theophylline on renin section were studied in relation to renal hemodynamic responses in anesthetized dogs. The intrarenal infusion of glucagon (0.5 microgram/kg/min) increased heart rate, renal blood flow, glomerular filtration rate and urine flow without any effect on renin secretion, but at a higher dose (1.0 microgram/kg/min) it increased renin secretion significantly. Theophylline (0.1 mg/kg/min) did not affect renal hemodynamics but caused a slight increase in renin secretion after 30--60 min infusion. The combined infusion of glucagon (0.5 microgram/kg/min) with theophylline (0.1 mg/kg/min) increased renin secretion markedly, although it produced renal hemodynamic changes similar to those induced by glucagon alone. These effects were not suppressed by d,l-propranolol (1.0 microgram/kg/min). It is suggested that the increase in renin secretion caused by the combined infusion of glucagon and theophylline resulted mainly from an increase in cyclic AMP in the juxtaglomerular cells, and not from stimulation of beta-adrenoceptors.
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PMID:Effect of glucagon on renin secretion in the dog. 21 14

Dispersed mucosal cells (approx. 70% parietal cells) prepared from guinea pig stomach maintained their cellular concentration of potassium (65--80 nmol potassium/10(6) cells) for at least 5 h in vitro. Uptake of 42K by dispersed gastric mucosal cells depended on temperature, H+ concentration and oxidative metabolism. Carbachol and, in some instances, gastrin caused a 40--50% increase in cellular uptake of 42K as a consequence of the ability of these agents to increase 42K influx. Ouabain reduced uptake of 42K by 70% but did not alter the effect of carbachol. Cellular uptake of 42K was not altered by histamine, prostaglandin, E1, glucagon, secretin, vasoactive intestinal peptide or C-terminal octapeptide of cholecystokinin. Uptake of 42K was also increased by dibutyryl cyclic AMP or dibutyryl cyclic GMP but not by cyclic AMP, cyclic GMP or their 8-bromo derivatives. Theophylline caused a small (10--15%) increase in 42K uptake and potentiated the increase caused by submaximal concentrations of carbachol. The increase in 42K uptake caused by either dibutyryl cyclic nucleotide and carbachol was additive.
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PMID:Potassium transport in dispersed mucosal cells from guinea pig stomach. 63 44


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