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)

Rabbits were anesthetized with urethane, and the concentration of 3',5' cyclic adenosine monophosphate (cAMP) in cerebrospinal fluid (CSF) was measured before and after injection into the cisterna magna of the following biologically active peptides and amines; adrenocorticotropin (ACTH), beta-melanocyte-stimulating hormone (beta-MSH), choroid plexus peptide IIF, arginine vasopressin, oxytocin, glucagon, epinephrine, serotonin, histamine, and acetylcholine. Only epinephrine and the lipolytic-melanotropic peptides ACTH, beta-MSH, and IIF influenced cAMP. Five to 500 mug ACTH caused a 3 to 10X increase in cAMP within 30 min; the concentration of nucleotide returned to baseline within 60-90 min after 5 or 50 mug, and remained elevated for at least 120 min after 500 mug. Effects of the same magnitude and tempo as those caused by 5 to 500 mug ACTH were produced by .1 to 10 mug beta-MSH and 5 to 500 mug IIF. Epinephrine at doses of 5 to 500 mug caused rises in cAMP of similar degree as the same dose of ACTH or peptide IIF, but the peak value was not reached until 60 to 90 min after injection.
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PMID:Effect of intrathecal injection of melanotropic-lipolytic peptides on the concentration of 3',5' cyclic adenosine monophosphate in cerebrospinal fluid. 17 24

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release. 17 62

Isolated adipocytes, incubated in the presence of extracellular 32Pi to steady state 32P incorporation into cellular phosphopeptides, were exposed to hormones for 5 min. Epinephrine (10(-6) M) stimulated 32P incorporation into at least 12 major phosphopeptides, distributed in the cytoplasm, endoplasmic reticulum, and plasma membrane. Quantitatively pre-eminent among these were peptides of molecular weight 123,000 and 69,000, each located both in the cytoplasm and endoplasmic reticulum. The effect of epinephrine (10(-7) M) on 32P incorporation into these two peptides was augmented by theophylline (10(-3) M) in a synergistic fashion. Norepinephrine, dibutyryl N6,O2'-dibutyryl adenosine 3':5'-monophosphate, adrenocorticotropic hormone (ACTH) (synthetic 1 to 24 fragment), and glucagon mimicked the effect of epinephrine. Insulin modified adipocyte peptide phosphorylation in two ways. When present as the sole hormone, insulin (100 microunits/ml) consistently and selectively stimulated the 32P incorporation into a peptide of molecular weight 123,000 (endoplasmic reticulum, cytoplasm) without significant alteration in the 32P content of any other major peptide. A second effect of insulin was evident when epinephrine (10(-6) M) was present simultaneously. Insulin significantly inhibited the epinephrine-stimulated phosphorylation of the molecular weight 69,000 (endoplasmic reticulum, cytoplasm) and 26,000 (plasma membrane) peptides. Nevertheless, persistence of insulin-stimulated phosphorylation of the 123,000 peptide in the presence of epinephrine was shown by a 32P content of this peptide that was greater in the presence of both hormones than with either individually. These findings indicate that in intact adipocytes: (a) epinephrine acutely alters the phosphorylation of a large number of adipocyte peptides, partly at least, via activation of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase; (b) insulin opposes several epinephrine-stimulated phosphorylations in a manner consitent with its ability to lower epinephrine-stimulated intracellular cyclic AMP accumulation in adipocytes; and (c) insulin, in addition, exerts a unique stimulatory effect on adipocyte peptide phosphorylation that is independent of its effects on cyclic AMP metabolism and may be medicated by the generation of an as yet undefined intracellular "messenger" unique to insulin.
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PMID:Effects of epinephrine and insulin on phosphopeptide metabolism in adipocytes. 17 55

1. Epinephrine-induced increase in rat liver cyclic AMP in vivo was potentiated when the circulating insulin was suppressed by injection of anti-insulin serum or by induction of diabetes. Consequently, phosphorylase was activated, glycogen synthetase was inactivated and glycogen accumulation induced by glucose load was prevented by epinephrine in the insulin-deficient rats to a much larger extent than in normal rats. 2. Insulin lack was effective in potentiating epinephrine-induced increase in liver and muscule cyclic AMP even after the treatment of rats with theophylline; the potentiation could not be solely accounted for by the inhibition of cyclic AMP phosphodiesterase. Thus, it is likely that insulin lack enhaces epinephrine activation of adenylate cyclase. 3. Unlike epinephrine, glucagon increased liver cyclic AMP to essentially the same extent whether the rat was treated with anti-insulin serum or not. 4. Based on the difference in dose-response curves between normal and insulin-deficient rats, a possibility is discussed that there are two adenylate cylase in the liver with higher and lower affinities for epinephrine and that circulating insulin blocks the high affinity enzyme selectively.
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PMID:Attenuation of epinephrine-induced increase in liver cyclic AMP by endogeneous insulin in vivo. 18 27

Glucagon causes a rapid activation of cAMP-dependent protein kinase in rat liver parenchymal cells which correlates well with the accumulation of cAMP. Full activation of phosphorylase or inactivation of glycogen synthase is achieved with half-maximal or less activation of protein kinase. Epinephrine stimulates glycogen breakdown in these cells mainly by mechanisms involving alpha-adrenergic receptors and not beta-receptors. Activition of alpha-receptors results in rapid activation of phosphorylase and inactivation of glycogen synthase without accumulation of cAMP or activation of cAMP-dependent protein kinase. Activation of beta-receptors causes a transient rise in cAMP and a short-lived activation of protein kinase with correspondingly little stimulation of glycogenolysis.
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PMID:Studies on the role of cAMP-dependent protein kinase in the actions of glucagon and catecholamines on liver glycogen metabolism. 18 93

In liver cells isolated from fed female rats, glucagon (290nM) increased adenosine 3':5'-monophosphate (cyclic AMP) content and decreased cyclic AMP binding 30 s after addition of hormones. Both returned to control values after 10 min. Glucagon also stimulated cyclic AMP-independent protein kinase activity at 30 s and decreased protein kinase activity assayed in the presence of 2 muM cyclic AMP at 1 min. Glucagon increased the levels of glycogen phosphorylase a, but there was no change in total glycogen phosphorylase activity. Glucagon increased glycogen phosphorylase a at concentrations considerably less than those required to affect cyclic AMP and protein kinase. The phosphodiesterase inhibitor, 1-methyl-3-isobutyl xanthine, potentiated the action of glucagon on all variables, but did not increase the maximuM activation of glycogen phosphorylase. Epinephrine (1muM) decreased cyclic AMP binding and increased glycogen phosphorylase a after a 1-min incubation with cells. Although 0.1 muM epinephrine stimulated phosphorylase a, a concentration of 10 muM was required to increase protein kinase activity. 1-Methyl-3-isobutyl xanthine (0.1 mM) potentiated the action of epinephrine on cyclic AMP and protein kinase. (-)-Propranolol (10muM) completely abolished the changes in cyclic AMP binding and protein kinase due to epinephrine (1muM) in the presence of 0.1mM 1-methyl-3-isobutyl xanthine, yet inhibited the increase in phosphorylase a by only 14 per cent. Phenylephrine (0.1muM) increased glycogen phosphorylase a, although concentrations as great as 10 muM failed to affect cyclic AMP binding or protein kinase in the absence of phosphodiesterase inhibitor. Isoproterenol (0.1muM) stimulated phosphorylase and decreased cyclic AMP binding, but only a concentration of 10muM increased protein kinase. 1-Methyl-3-isobutyl xanthine potentiated the action of isoproterenol on cyclic AMP binding and protein kinase, and propranolol reduced the augmentation of glucose release and glycogen phosphorylase activity due to isoproterenol. These data indicate that both alpha- and beta-adrenergic agents are capable of stimulating glycogenolysis and glycogen phosphorylase a in isolated rat liver cells. Low concentrations of glucagon and beta-adrenergic agonists stimulate glycogen phosphorylase without any detectable increase in cyclic AMP or protein kinase activity. The effects of alpha-adrenergic agents appear to be completely independent of changes in cyclic AMP protein kinase activity.
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PMID:Activation of protein kinase and glycogen phosphorylase in isolated rat liver cells by glucagon and catecholamines. 18 18

Epinephrine, insulin, glucagon and theophylline produced a significant increase in the cAMP level of Tetrahymena, while the enhancing effect of TSH was not significant. The experimental results suggest that Tetrahymena possesses receptors for hormones of higher animals, but has no receptor for the nonsense hormone TSH. The cAMP enhancing effect shown by many hormones of higher animals irrespective of their different functions indicates that apart from the general mediator action of cAMP, some special mediation is also taking place.
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PMID:Effect of vertebrate hormones on the cyclic AMP level in Tetrahymena. 19 Aug 36

In normal fed rats, glycogen synthase D phosphatase activity in a glycogen pellet preparation was only partially inhibited (approximately 50%) by high concentrations of EDTA. However, the proportion of phosphatase activity inhibited by EDTA was markedly and rapidly (15 s) increased following glucagon or cAMP administration. Epinephrine administration did not alter the proportion of activity inhibited by EDTA. Glucose administration rapidly (2 min) reduced the proportion of synthase phosphatase activity inhibitable by EDTA. That is, the effect of glucose was just the opposite of that produced by glucagon or cAMP. Insulin administration had no effect on phosphatase activity. Synthase phosphatase activity assayed in the absence of EDTA was similar in all groups except for a moderate increase after glucose administration. Addition of Mg2+ completely reversed EDTA inhibition. Phosphorylase phosphatase activity in each group was not modified by addition of EDTA, although the percentage of phosphorylase in the alpha form was higher in glucagon-treated and lower in the glucose-treated animals as expected. These data suggest the presence of rapidly interconvertible forms of either synthase phosphatase or its substrate synthase D, detectable as a change in EDTA inhibitability and subject to glucose and glucagon control.
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PMID:In vivo glucose-, glucagon-, and cAMP-induced changes in liver glycogen synthase phosphatase activity. 20 88

Epinephrine rapidly activates phosphorylase in hepatocytes, mainly by a mechanism(s) involving alpha-adrenergic and not beta-adrenergic receptors. The alpha-adrenergic mechanism does not involve accumulation of cAMP or activation of cAMP-dependent protein kinase. It is impaired when hepatocytes are depleted of calcium by EGTA treatment and is rapidly restored by readdition of calcium. Basal phosphorylase is also lowered by calcium deficiency and rapidly increased by calcium but not other divalent cations. The divalent cation ioniphore A23187 increases phosphorylase a levels in hepatocytes in a calcium-dependent manner. Calcium deficiency does not modify the effects of glucagon, cAMP, or beta-adrenergic activation on phosphorylase. Activation of alpha-adrenergic receptors rapidly increases 45Ca fluxes in hepatocytes. Glucagon produces similar effects, but supraphysiological concentrations are required. The hypothesis is advanced that alpha-adrenergic activation of phosphorylase involves alterations in cell calcium such that there is an increase in cytosolic Ca2+ concentration leading to increased phosphorylase kinase activity. Epinephrine induces greater cAMP accumulation in calcium-depleted cells than in normal cells. The effect is mediated by alpha-adrenergic and not beta-adrenergic receptors. Calcium deficiency also cuases cAMP accumulation in hepatocytes incubated with phenylephrine but does not modify the responses of the cells to isoproterenol, glucagon, or cAMP. Low concentrations of calcium rapidly reverse alpha-adrenergic receptor-mediated cAMP accumulation in calcium-depleted cells. The hypothesis is advanced that calcium normally exerts an inhibitory effect on a linkage between alpha-adrenergic receptors and adenylate cyclase in hepatocytes.
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PMID:Mechanisms of catecholamine actions on liver carbohydrate metabolism. 20 89

1. In frog liver, tyrosine aminotransferase is located mainly in cytoplasm. The enzyme is an anionic protein of mol. wt. 115 000 daltons, specific toward 2-oxoglutarate. The enzyme separates on ion-exchange chromatography into two active forms. 2. Administration of triiodotyronine in vivo induces the activity of the enzyme. Epinephrine and glucagon have no effect, and cAMP and insulin repress this activity by about 70%. 3. Triiodotyronine stimulates incorporation of [14C]leucine into protein, and the amount of the enzyme in the nacent polysome-bound protein is considerably increased.
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PMID:Tyrosine aminotransferase in frog liver. 23 10


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