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 adaptation of newborn mannals to extrauterine life depends in large part on the maturation of biochemical and physiological functions during perinatal development. Hormones such as glucocorticoids, catecholamines and glucagon can stimulate enzyme induction during development; on the other hand, insulin has been shown to antagonize these stimulatory effects. Only the surface of the problem of hormonal regulation of enzyme differentiation during the perinatal period has been reached, especially as regards human development. Each enzyme presents unique problems of chemical regulation; the functional consequences of these factors are not exactly the same in each tissue and perhaps not in each species. The possibility of using inducing agents such as hormones, drugs and substrates to promote biochemical enzyme differentiation is a new and exciting aspect which needs to be explored further as a means of facilitating survival and ensuring optimal extrauterine development of the immaturely born human infant or the full-term infant with delayed-enzymic development. However, any intervention in the carefully programmed interplay of different hormones which regulate normal enzymic adaptation and development during the perinatal period should be undertaken only after careful consideration. The possibilities of long-term harm must be weighed against short-term benefits.
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PMID:Hormonal regulation of perinatal enzyme differentiation in the mammalian liver. 3 54

The administration of monosodium-L-glutamate (MSG) during the neonatal period is known to result in central nervous system lesions in the arcuate nucleus of the hypothalamus and the retina. Rodents so treated exhibit behavioral deficts and endocrinopathies including obesity, hypogonadism, hypothyroidism, pituitary atrophy, tail automutilation and diminished locomotor activity. Assessment of endocrine status revealed normal serum levels of glucagon, thyroid-stimulating hormone and luteinizing hormone, and diminished levels of thyroid hormones and growth hormone in MSG-treated rats. Prolactin levels were elevated in the glutamate-treated male rats. Within the brain hypothalamic levels of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, and somatostatin were unchanged. Measurement of neurotransmitters and neurotransmitter-related enzymes in individual hypothalamic nuclei derived from MSG-treated rats revealed normal levels of norepinephrine, serotonin and glutamic acid decarboxylase, but reduced levels of choline acetyltransferase and dopamine in the arcuate nucleus and median eminence. Histochemical methods for visualization of dopamine and acetylcholinesterase in the mediobasal hypothalamus confirmed these findings. The MSG-treated animals exhibited a normal diurnal rhythm of pineal serotonin N-acetyltransferase activity. These data indicate that the MSG-induced endocrine deficiency syndrome results at least partly from destruction of cholinergic and dopamingeric tuberoinfundibular systems in the hypothalamus.
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PMID:Models of neuroendocrine regulation: use of monosodium glutamate as an investigational tool. 3 35

The regulation of tyrosine aminotransferase activity by glucocorticoids and cyclic AMP was investigated in isolated liver parenchymal cell suspensions. The induction and maintenance of elevated levels of tyrosine aminotransferase activity in liver cells were completely dependent upon the presence of both the synthetic glucocorticoid, dexamethasone, and glucagon of dibutyryl cyclic AMP. No induction was observed when any of these compounds were tested alone. Immunotitration experiments revealed that the 6- to 7-fold increase in tyrosine aminotransferase activity following the addition of dexamethasone and glucagon was accompanied by a parallel increase in the amount of immunologically reactive enzyme protein. Pulse-labeling experiments established that this increase in enzyme protein could be fully accounted for by a corresponding increase in rate of synthesis of tyrosine aminotransferase. Neither hormone had any effect on the rate of degradation of the enzyme. The increase in tyrosine aminotransferase synthesis evoked by the presence of both hormones was blocked by the addition of actinomycin D or cycloheximide to the medium, demonstrating that RNA and protein synthesis were required for the induction of enzyme activity. By varying the time and order of addition of the inducers and inhibitions, evidence was obtained that the hormones act sequentially. The steroid hormone acts first, presumably to increase the level of functional tyrosine aminotransferase mRNA or its precursor. The processing of this precursor to a translatable form or the specific translation of tyrosine aminotransferase mRNA is apparently dependent upon a specific cyclic AMP-controlled process. In vivo experiments demonstrated that both glucocorticoids and cyclic AMP increase the level of functional tyrosine aminotransferase mRNA in the liver. The actions of the steroid hormone and cyclic nucleotide were blocked by alpha amanitin, establishing the requirement for ongoing gene transcription. The protein synthesis inhibitors, cycloheximide, emetine, and puromycin, were as effective as cyclic AMP in increasing tyrosine aminotransferase mRNA activity. The action of these inhibitors is probably related to their ability to elevate hepatic intracellular cyclic AMP levels, thus mimicking cyclic AMP administration. Extension of these in vivo studies to isolated liver cells will provide a valuable system for investigating the regulation of gene expression by glucocorticoids and cyclic AMP.
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PMID:Multihormonal control of tyrosine aminotransferase in isolated liver cells. 4 Jan 15

Intraperitoneal injection of neonatal rats with glucocorticoid hormones causes precocious development of hepatic cytochrome P-450. Glucagon injection fails to stimulate this cytochrome P-450 development. Adult liver cytochrome P-450 is less responsive to glucocorticoid stimulation than is that of neonatal rat liver. Adrenalectomy of prematurely delivered neonatal animals prevents the early postnatal development of cytochrome P-450. Glucocorticoids failed to increase cytochrome P-450 concentrations in foetal rat liver. These findings imply that, although glucocorticoids are mandatory regulatory factors controlling cytochrome P-450 development, they are not themselves the 'trigger' initiating onset of that development.
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PMID:Precocious development of cytochrome P-450 in neonatal rat liver after glucocorticoid treatment. 4 May 49

The effects of 5-hydroxytryptamine (5-HT) on plasma cyclic AMP (cAMP) and glucose concentrations were studied in rats in vivo. 5-HT injected i.p. increased plasma cAMP and glucose. Injections of propranolol, hexamethonium, and cyproheptadine inhibited the 5-HT-induced increase in glucose but not in cAMP. Atropine did not inhibit the action of 5-HT. These effects of 5-HT were not seen in adrenomedullectomized rats, and 5-HT did not elevate the concentration of plasma cAMP in anti-glucagon antiserum-injected rats. These results confirm the previously reported finding that 5-HT-induced increase in blood glucose is mediated via adrenaline released from adrenal medulla by 5-HT and suggest that the increase in plasma cAMP, induced by 5-HT, is due to glucagon released by an unknown factor, or factors other than adrenaline released from the adrenal medulla by 5-HT.
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PMID:Effect of 5-hydroxytryptamine on blood glucose and cyclic AMP in the rat. 4 Oct 61

1. Adenylate cyclase (EC 4.6.1.1) activity was characterized in human liver, and its subcellular distribution compared with that of three other potential enzyme markers of the pericellular membrane: leucine aminopeptidase (EC 3.4.11.1), gamma-glutamyltransferase (EC 2.3.2.2) and 5'-nucleotidase (EC 3.1.3.5). Although these three enzyme activities were detected in each of the subcellular fractions studied, 85% of the total adenylate cyclase activity was found in the 1000 g pellet ('nuclear' fraction) with a threefold increase in specific activity as compared with the homogenate. No adenylate cyclase activity existed in the 150 000 g supernatant fraction. 2. In the 'nuclear' fraction, adenylate cyclase activity was increased in a dose-dependent fashion by glucagon with a half-maximal stimulation at 10 nmol/l and a maximal four- to seven-fold increase at 1 mumol/l. Catecholamines activated adenylate cyclase 2.5- to three-fold, with an order of potency (protokylol greater than isoprenaline greater than adrenaline greater than noradrenaline) typical of a beta 2-adrenoreceptor. Prostaglandin E1 and NaF also stimulated cyclase two- and four-fold respectively. Insulin, serotonin, dopamine, thyroid-stimulating hormone and ACTH had no effect. Adenosine provoked a weak inhibition at 0.1 mmol/l. Finally guanosine triphosphate and 5'-guanylyl imidodiphosphate induced a marked increase in basal activity, four- and eight-fold respectively, but both reduced the relative increase in enzyme activity due to glucagon or adrenaline. 3. Cyclase from foetal liver (12--16 weeks old) and cirrhotic adult liver appeared to behave similarly to that from normal liver; however, foetal cyclase was more active, and cirrhotic enzyme less active than normal adult liver. Both systems responded to catecholamines via a beta 2-adrenoreceptor. 4. These results validate the use of rat liver adenylate cyclase as a tool for pharmacological and physiological studies.
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PMID:The adenylate cyclase system in human liver: characterization, subcellular distribution and hormonal sensitivity in normal or cirrhotic adult, and in foetal liver. 4 65

Chick liver cell monolayers synthesize fatty acids at in vivo rates and are responsive to insulin and glucagon. High rates of fatty acid synthesis are maintained with insulin present and lost slowly without insulin. Glucagon or 3',5'-cyclic AMP cause immediate cessation of fatty acid synthesis. The site of inhibition appears to be cytoplasmic acetyl-CoA carboxylase which catalyzes the first committed step of fatty acid synthesis. Liver carboxylase exists either as catalytically inactive protomers or active filamentous polymers. Citrate, an allosteric activator of the enzyme, is required for both catalysis and polymerization. Glucagon and cAMP cause an immediate decrease in the cytoplasmic citrate concentration of chick liver cells apparently by inhibiting the conversion of glucose to citrate at the phosphofructokinase reaction. Since fatty acid synthesis and citrate level are closely correlated, citrate appears to be a feed-forward activator of the carboxylase in vivo. Compelling evidence indicates that carboxylase filaments are present in the intact cell when citrate levels are high and depolymerize when citrate levels fall. Hence, carboxylase activity and fatty acid synthetic rate appear to be determined by cytoplasmic citrate level.
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PMID:Hormonal regulation of acetyl-CoA carboxylase activity in the liver cell. 4 83

Particulate fractions of myocardium taken from spontaneously hypertensive rats (SHR) contained an adenylate cyclase system that was less responsive than normotensive Wistar Kyoto rats to norepinephrine, isoproterenol (mixed beta-agonist), salbutamol (beta 2-agonist), dobutamine (beta 1-agonist), dopamine, histamine, and glucagon. Addition of 5'-guanylylimidodiphosphate to the SHR myocardial preparation again yielded a lessened sensitivity to all agents except norepinephrine, dopamine, and histamine. Chronic treatment of SHR with clonidine and a high dose of propranolol produced a cardiac enzyme that was insensitive to activation by norepinephrine. Similar treatment with a low dose of propranolol did not alter myocardial responses to norepinephrine.
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PMID:Alterations in myocardial adenylate cyclase in spontaneously hypertensive rats. 4 30

The present study was conducted to determine the effects of beta-adrenergic stimulation on plasma glucose and glucagon (IRG) levels in Japanese quail. Isoproterenol, epinephrine and three relatively selective beta-adrenoceptor agonists (terbutaline, salbutamol and reproterol) produced dose-related hyperglycemia and hypoglucagonemia. This study demonstrates that beta-adrenoceptor agonists produce hyperglycemia in birds as they do in mammals, but that the rise in plasma glucose in birds, unlike mammals, is accompanied by a profound fall in plasma IRG levels.
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PMID:Effect of beta-adrenergic drugs on plasma glucose and glucagon in Japanese quail: a preliminary report. 4 57

To examine the mechanism of the recently reported effect of an acidified intragastric test meal on insulin release and glucose homeostasis, a liver extract test meal at either pH 2 or pH 7 was instilled into the stomach of normal dogs and dogs with a chemical sympathectomy or indomethacin-induced prostaglandin deficiency, all of which had a bisected pylorus and gastric fistula. In the normal dogs the instillation of the liver meal at pH 2 elicited a significant rise in plasma glucose, glucagon and insulin levels, while in response to the meal at pH 7 only glucagon rose significantly. This was not altered in chemically sympathectomized dogs, nor during the infusion of indomethacin. In all experiments gastrin or gastric glucagon release in response to the meal at pH 2 was either lower than or similar to the response to the meal at pH 7. These data suggest that the influence of the stomach upon islet cell function and glucose homeostasis does not depend on either adrenergic innervation or the presence of prostaglandings, but rather is mediated by a yet undetermined mechanism.
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PMID:Sympathectomy and prostaglandin deficiency do not prevent gastrogenic hyperglycaemia and hyperinsulinaemia. 4 43


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