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 effect of hormones on cell volume was studied in isolated perfused rat liver by assessing the intracellular water space as the difference between a [3H]inulin- and a [14C]urea-accessible space. The intracellular water space (control value 559 +/- 7 microliters/g of liver; n = 88) increased on addition of insulin (35 nM) or phenylephrine (5 microM) by 12 or 8% respectively, whereas it decreased with cyclic AMP (cAMP; 50 microM), glucagon (100 nM) or adenosine (50 microM) by 9, 13 or 6% respectively. Both insulin and glucagon exerted half-maximal effects on cell volume and cellular K+ balance at hormone concentrations found physiologically in the portal vein. Adenosine-induced cell shrinkage was explained by a net K+ release from the liver. Phenylephrine (5 microM) led to cell swelling by about 8%, which was additive to insulin-induced swelling. Extracellular ATP (20 microM) induced cell shrinkage by about 6%; this was additive to adenosine-induced shrinkage. Vasopressin (15 nM) did not appreciably change cell volume, but induced marked cell shrinkage when glucagon or cAMP was present. Insulin- and phenylephrine-induced cell swelling was counteracted by cAMP. Hormone-induced changes of intracellular water space could sufficiently explain accompanying liver mass changes induced by glucagon, cAMP, adenosine or vasopressin, but not those by phenylephrine and extracellular ATP. The data show that liver cell volume is subject to hormonal regulation, in part owing to modification of cellular K+ balance. Glucagon- and insulin-induced cell volume changes occur already in the presence of physiological hormone concentrations. The effects of Ca2(+)-mobilizing hormones on cell volume are not uniform. In view of the recently established role of cell volume changes in modulating liver cell function, the present findings open a new perspective on the mechanisms of hormone action in liver, underlining our previous hypothesis that cell volume changes may represent a 'second messenger' of hormone action.
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PMID:Regulation of cell volume in the perfused rat liver by hormones. 166 Feb 61

1. In isolated hepatocytes prelabelled with [14C]-arachidonic, -stearic, -linoleic, -oleic or -palmitic acids, vasopressin increased the amount of radioactivity present in diacylglycerols. The largest increase was observed in cells labelled with arachidonic or stearic acids. 2. In cells prelabelled with [14C]- or [3H]-arachidonic acid, the onset of the increase in radioactivity in diacylglycerols induced by vasopressin was slow, the increase was partly dependent on the presence of extracellular Ca2+, and was associated with an increase in radioactivity present in phosphatidic acid which was more rapid in onset. Vasopressin decreased the amount of [3H]arachidonyl-phosphatidylinositol 4,5-bisphosphate, but the magnitude of this decrease was less than 10% of the observed increase in radioactivity in [3H]arachidonyl-diacylglycerol. 3. The concentration of vasopressin which gave half-maximal increase in [14C]arachidonyl-diacylglycerol at low extracellular Ca2+ was 10-fold higher than that which gave half-maximal stimulation of 45Ca2+ efflux. Phenylephrine, but not glucagon, also increased the amount of [14C]arachidonyl-diacylglycerol. 4. It is concluded that an early action of vasopressin on the liver cell is to increase the flux of carbon from phospholipids, including the phosphoinositides, to diacylglycerols.
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PMID:Evidence from studies employing radioactively labelled fatty acids that the stimulation of flux through the diacylglycerol pool is an early action of vasopressin on hepatocytes. 311 41

Phenylephrine, vasopressin and glucagon each increased the amount of active (dephospho) pyruvate dehydrogenase (PDHa) in isolated rat hepatocytes. Treatment with 4 beta-phorbol 12-myristate 13-acetate (PMA) opposed the increase in PDHa caused by both phenylephrine and glucagon, but had no effect on the response to vasopressin: PMA alone had no effect on PDHa. As PMA is known to prevent the phenylephrine-induced increase in cytoplasmic free Ca2+ concentration ([Ca2+]c) and to diminish the increase [Ca2+]c caused by glucagon, while having no effect on the ability of vasopressin to increase [Ca2+]c, these data are consistent with the notion that in intact cells an increase in [Ca2+]c results in an increase in the mitochondrial free Ca2+ concentration, which in turn leads to the activation of PDH. In the presence of 2.5 mM-Ca2+, glucagon caused an increase in NAD(P)H fluorescence in hepatocytes. This increase is taken to reflect an enhanced activity of mitochondrial dehydrogenases. PMA alone had no effect on NAD(P)H fluorescence; it did, however, compromise the increase produced by glucagon. When the extracellular free [Ca2+] was decreased to 0.2 microM, glucagon could still increase NAD(P)H fluorescence. Vasopressin also increased fluorescence under these conditions; however, if vasopressin was added after glucagon, no further increase in fluorescence was observed. Treatment of the cells with PMA resulted in a smaller increase in NAD(P)H fluorescence on addition of glucagon: the subsequent addition of vasopressin now caused a further increase in fluorescence. Changes in [Ca2+]c corresponding to the changes in NAD(P)H fluorescence were observed, again supporting the idea that [Ca2+]c indirectly regulates intramitochondrial dehydrogenase activity in intact cells. PMA alone had no effect on pyruvate kinase activity, and the phorbol ester did not prevent the inactivation caused by glucagon. The latter emphasizes the different mechanisms by which the hormone influences mitochondrial and cytoplasmic metabolism.
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PMID:The glucagon-induced activation of pyruvate dehydrogenase in hepatocytes is diminished by 4 beta-phorbol 12-myristate 13-acetate. A role for cytoplasmic Ca2+ in dehydrogenase regulation. 359 19

Thiol and glutathione (GSH) efflux across the sinusoidal plasma membrane in isolated perfused rat liver was stimulated by addition of hormones such as vasopressin, phenylephrine and adrenaline, whereas glucagon or dibutyryl cyclic AMP were without effect. Phenylephrine and adrenaline effects were sensitive to prazosin and phentolamine, respectively. The increase in thiol efflux was largely accounted for by an increase in GSH efflux. Thiol efflux and the hormone effects were abolished in GSH-depleted liver. Biliary GSH efflux was diminished upon hormone addition. The newly discovered hormone-dependence of GSH release across the sinusoidal plasma membrane may explain the known loss of GSH during conditions of experimental shock (traumatic or endotoxin) and stress and peripheral inflammation.
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PMID:Hepatic thiol and glutathione efflux under the influence of vasopressin, phenylephrine and adrenaline. 399 71

Addition of phenylephrine to isolated perfused rat liver is followed by an increased 14CO2 production from [1-14C]glutamate, [1-14C]glutamine, [U-14C]proline and [3-14C]pyruvate, but by a decreased 14CO2 production from [1-14C]pyruvate. Simultaneously, there is a considerable decrease in tissue content of 2-oxoglutarate, glutamate and citrate. Stimulation of 14CO2 production from [1-14C]glutamate is also observed in the presence of amino-oxyacetate, suggesting a stimulation of glutamate dehydrogenase and 2-oxoglutarate dehydrogenase fluxes by phenylephrine. Inhibition of pyruvate dehydrogenase flux by phenylephrine is due to an increased 2-oxoglutarate dehydroxygenase flux. Phenylephrine stimulates glutaminase flux and inhibits glutamine synthetase flux to a similar extent, resulting in an increased hepatic glutamine uptake. Whereas the effects of NH4+ ions and phenylephrine on glutaminase flux were additive, activation of glutaminase by glucagon was considerably diminished in the presence of phenylephrine. The reported effects are largely overcome by prazosin, indicating the involvement of alpha-adrenergic receptors in the action of phenylephrine. It is concluded that stimulation of gluconeogenesis from various amino acids by phenylephrine is due to an increased flux through glutamate dehydrogenase and the citric acid cycle.
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PMID:Effect of phenylephrine on glutamate and glutamine metabolism in isolated perfused rat liver. 614 74

The short-term controls of glycogen synthase [EC 2.4.1.11] and glycogen phosphorylase [EC 2.4.1.1] by major regulators, such as insulin, glucose, catecholamine, and glucagon, were compared in a simple, yet organized experimental system, i.e., adult rat hepatocytes in primary culture. Glycogen synthase was activated by glucose markedly and dose-dependently (5-40 mM), but insulin alone (1 X 10(-8) M) activated this enzyme only two-fold. Therefore, activation of the enzyme by the two regulators together was mostly due to activation by glucose. Glucagon at a concentration of 5 X 10(-10) M suppressed this activation almost completely. Glucagon at this concentration activated phosphorylase considerably and this activation was slightly inhibited by insulin. Phenylephrine also activated phosphorylase, and this activation was inhibited by phenoxybenzamine or prazosin, suggesting that activation by catecholamine is through the alpha 1-adrenergic receptor. Similarly a high concentration of glucose diminished the effects of glucagon and phenylephrine. These results suggest that in rat liver, glycogen metabolism is controlled mainly by glucagon, catecholamine, and glucose; the former two activate phosphorylase and inactivate synthase, while glucose activates synthase strongly and inactivates phosphorylase partially. Insulin plays a minor role in both reactions. Thus, the liver is primarily an organ for glucose production, which is regulated by hormones, not for glycogen storage, which is increased only by a high glucose concentration in the portal blood.
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PMID:Glucagon and glucose as major regulators of glycogen metabolism in primary cultured rat hepatocytes. 643 74

1. A method is described for efficient and rapid isolation of viable hepatocyte suspensions from chick embryos in the last few days of incubation. 2. Although qualitatively similar, quantitative differences exist in the hormonal control of glycogen metabolism between embryonic and hatched chicks. 3. Glucagon and adrenaline activate glycogenolysis. 4. Insulin did not inhibit basal or glucagon-stimulated glycogenolysis. 5. Phenylephrine (an alpha-adrenergic agonist), angiotensin and vasopressin, all of which activate glycogen breakdown in rat liver through a Ca2+-dependent mechanism, were without effect on chick embryo hepatocytes.
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PMID:Hormonal regulation of glycogen metabolism in hepatocyte suspensions isolated from chicken embryos. 680 8

Phenylephrine (1.5 x 10(-6) M) administered to perfused livers from fed rats gave rise to a rapid, parallel increase in oxygen uptake and glucose output. The time of onset for oxygen uptake was 9.9 +/- 0.4 s following phenylephrine administration, and immediately preceded glucose output which occurred at 11.6 +/- 0.5 s. Near-maximal effects were observed 50 s following alpha-agonist treatment. Both responses appear to be mediated by alpha- 1-adrenergic receptors. The mitochondrial respiratory chain blockers antimycin A and rotenone, inhibited the alpha-agonist-induced oxygen uptake and glycogenolytic responses at inhibitor concentrations similar to those required to block uncoupler-stimulated respiration in the intact perfused liver. Oligomycin and carboxyatractyloside also inhibited the phenylephrine-induced respiratory response. Vasopressin (1 milliunit/ml), and angiotensin II (6 x 10(-9) M) had effects similar to phenylephrine in the perfused liver which also were prevented by the prior administration of antimycin A and rotenone. In contrast, glucagon-induced (10(-8) M) glycogenolysis proceeded in the absence of large changes in respiration, was slower in onset (26.1 +/- 4.2 s following hormone administration), and was not inhibited by mitochondrial respiratory blockers. These data indicate that glycogenolysis induced by alpha-adrenergic agonists, vasopressin, and angiotensin II is associated with a large increase in mitochondrial respiration, that may play a role in a general, as yet undefined mechanism whereby these agents stimulate glycogenolysis in rat liver.
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PMID:Studies on alpha-adrenergic-induced respiration and glycogenolysis in perfused rat liver. 705 51

We have adapted the high-resolution electrophoretic technique of O'Farrell to analyze phosphorylated proteins from rat hepatocytes. Total proteins were extracted from rat hepatocytes which had been incubated in the presence of [32P]phosphate and with two types of stimuli: glucagon on the one hand and the Ca2+-linked hormones on the other hand. About 200 phosphorylated polypeptides have been separated. Glucagon modifies the incorporation of [32P]phosphate in at least 17 polypeptides and dibutyryladenosine 3',5'-monophosphate mimics this hormonal effect, implying a common mechanism of action. Phenylephrine (in the presence of the beta-antagonist propranolol), vasopressin and angiotensin all modify the incorporation of [32P]phosphate in about 13 polypeptides; since the Ca2+ ionophore A23 187 reproduces the effect of these agents it may be concluded that Ca2+ mediates their effect. Not all the substrates affected by the two types of hormones are identical. Both types of stimuli increase the phosphorylation of a same set of seven proteins and decrease the phosphorylation of a same set of three proteins but seven proteins have their phosphorylation uniquely enhanced by glucagon whereas three other specific proteins get more phosphorylated by the Ca2+ -linked hormones. The clear differences between the patterns of protein phosphorylation observed in the presence of glucagon and dibutyryladenosine 3',5'-monophosphate on the one hand and by the Ca2+-linked hormones on the other hand strongly suggest different mechanisms of action for these two types of stimuli.
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PMID:Pattern of protein phosphorylation in rat hepatocytes stimulated by glucagon or by the Ca2+-linked hormones. 714 Jul 54

The involvement of adenosine 3',5'-cyclic monophosphate (cAMP) in the stimulation of ventricular protein synthesis by aortic hypertension or adrenergic agonists in the adult rat heart was investigated. In either the retrogradely or anterogradely perfused heart, aortic hypertension increased protein synthesis rates by up to 19%. However, no changes in cAMP concentrations or in cAMP-dependent protein kinase activity ratios could be detected either at early (< 5 min) or late (90 min) time points. Although isoproterenol, 3-isobutyl-1-methylxanthine, or forskolin raised cAMP concentrations (by up to 4.5-fold) and cAMP-dependent protein kinase ratios (by up to 4-fold), protein synthesis rates were not increased; however, under some perfusion conditions, glucagon did stimulate protein synthesis by 25%. Epinephrine stimulated protein synthesis by up to 32%, an effect that was not prevented by propranolol. Phenylephrine also stimulated protein synthesis, an effect that was prevented by prazosin but was unaffected by yohimbine. These findings implicate the alpha 1-adrenoceptor in the regulation of cardiac protein synthesis. Because changes in adenine nucleotide concentrations were similar in hearts perfused with epinephrine or with the agents that raised cAMP, it is unlikely that adenine nucleotide depletion is responsible for the failure to observe effects of the latter group of agents on protein synthesis. Although isoproterenol or forskolin raised cAMP concentrations in isolated ventricular cardiomyocytes where ATP depletion was minimal, neither stimulated protein synthesis. alpha 1-Adrenergic agonists stimulate phosphoinositide hydrolysis in the heart (Brown, J. H., I. L. Buxton, and L. L. Brunton. Circ. Res. 57:532-537, 1985). Aortic hypertension doubled the rate of phosphoinositide hydrolysis in the perfused heart. We suggest that the phosphoinositide-linked signal transduction pathway is more likely to be involved in stimulation of cardiac protein synthesis by hypertension or adrenergic agonism than the adenylyl cyclase/cAMP-linked pathway.
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PMID:cAMP and protein synthesis in isolated adult rat heart preparations. 769 91


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