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)

(1) A system is described for studying the short-term effects of agents on proinsulin synthesis in vitro, as measured by the incorporation of [3H]leucine into isolated proinsulin. (2) Of the agents tested, glucose has the most marked, and apparently earliest, effect on proinsulin synthesis. (3) The adenyl cyclase system participates in the regulation of proinsulin synthesis since exogenous cyclic AMP, glucagon, and caffeine are stimulatory. When cyclic AMP is added to the medium in the presence of glucose, it is the most potent agent acting on the adenyl cyclase-phosphodiesterase system. (4) The addition of NADPH to isolated rat islets inhibits proinsulin and Bulk Protein synthesis in vitro.
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PMID:Regulation of proinsulin synthesis in isolated rat islets. 0 29

Both caffeine and theophylline, which were known to be potent inhibitors of cyclic-AMP phosphodiesterase, stimulated the incorporation of myoinositol into phosphatidylinositol in rat liver homogenate. However, cyclic-AMP had no effect. The effect of dibutyryl-cyclic-AMP differed with different concentrations. These results suggest that the stimulation cannot be explained by the increase in the amount of cyclic-AMP. This view was supported by the fact that papaverine, cyclic-AMP phosphodiesterase inhibitor, did not stimulate the incorporation and imidazole, the phosphodiesterase stimulator, did not inhibit the incorporation, and that adenylcyclase stimulators, epinephrine and glucagon, did not stimulate the incorporation.
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PMID:Studies on myoinositol. Effects of caffeine and theophylline on incorporation of myoinositol into phosphatidylinositol in rat liver homogenate. 17 40

N6,O2'-dibutyrylcyclo-3',5'-AMP injected to intact rats alone or in combination with theophylline increases the activity of guanidine acetate methyltransferase (GAMT) in liver and pancreas. Cyclic 3',5'-AMP and its dibutyryl analog administered immediately or two hours after the suturing of common bile duct (SCBD) stimulate the increase of pancreatic GAMT activity 2-3 fold. Glucagon, injected intraabdominally simultaneously with SCBD and administration of theophylline, dramatically increases the theophylline effect on the GAMT activity. The freezing of rat pancreas pretreated witn secretin, a hormone structurally similar to glucagon, results in a 1.5-2-fold increase of creatine synthesis from S-adenosylmethionine and guanidinacetic acid. An hour after glucagon administration to intact rats the GAMT activity of liver increases 9 times. The effect of glucagon is enhanced by insulin. Cycloheximide inhibits the increase of GAMT activity, induced by glucagon or a combination of glucagon and insulin. Experiments on tissue homogenates demonstrate that 3',5'-AMP in concentrations of 10(-8) --10(-2) M does not affect the GAMT activity or to some extent inhibits the enzyme. The homogenate incubation in a medium containing 10(-5) M epinephrine or 10(-7) M caffeine and 5 mM Mg2+ leads to an increase in the GAMT activity. Oligomycin removes the stimulating effects of caffeine and Mg2+ on the enzyme activation. This is probably due to the presence of 3',5'-AMP-dependent protein kinase in the mechanism of GAMT activation by cyclic AMP.
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PMID:[The stimulating effect of cyclic AMP, glucagon and insulin on guanidine acetate-N-methyltransferase activity in rat liver and pancreas]. 17 11

The actions of insulin and glucagon in the fetal lamb and regulation of their secretion from the fetal pancreas have been examined to assess the possible roles of these hormones in regulating glucose homeostasis in the lamb during fetal life. Much evidence indicates that insulin stimulated glucose utilization in the fetal lamb and that glucagon can promote mobilization of fetal liver glycogen. Glucose stimulates and adrenaline inhibits insulin secretion by fetal pancrease pieces in vitro from 50 days gestation onwards, but alanine and glycine have little effect on insulin release. Alanine and glycine stimulate glucagon secretion by fetal pancreas pieces in vitro from 50 days gestation. The effects are potentiated by caffeine. Adrenaline has a small stimulatory effect but glucagon release is not altered by glucose. In vivo adrenaline infusion increases fetal plasma glucagon concentrations but glycine infusion does not. Glycine infusion into post-natal lambs increases plasma glucagon. Fasting pregnant ewes for two days decreases plasma insulin but does not alter plasma glucagon in either ewe or fetus. The observations suggest insulin secretion in the fetal lamb is an important determinant of glucose uptake and utilization by the fetus during at least the last third of pregnancy. The quantitative importance of glucagon in regulating fetal hepatic glucose metabolism remains uncertain.
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PMID:Glucagon, insulin and glucose homeostasis in the fetal lamb. 61 10

We tested the hypothesis that increased plasma glucagon concentration resulting from portal-systemic shunting or liver dysfunction causes arterial vasodilation and thereby stimulates sodium retention in cirrhosis. Twenty-seven studies were performed in patients with alcoholic liver disease, 11 of whom had ascites. Liver function was quantitated as the elimination rate of antipyrine, caffeine, and stable isotopes of cholic acid administered both orally (2,2,4,4-2H) and intravenously (24-13C). Portal-systemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid. Cardiac output was measured by using Doppler echocardiography. Plasma glucagon concentration was increased in patients with ascites when compared with that in patients without ascites (474 +/- 180 pg/ml vs 245 +/- 120 pg/ml, p = 0.0007) but was unrelated to urinary sodium excretion, heart rate, mean arterial pressure, cardiac output, and systemic vascular resistance (r = -0.48, 0.35, -0.13, 0.18, and 0.22, respectively). Plasma glucagon concentration correlated with the half-lives of all model compounds (r = 0.58, p = 0.002; r = 0.62, p = 0.0008; r = 0.62, p = 0.001; and r = 0.64, p = 0.0005; for caffeine, antipyrine, oral and intravenous cholic acid, respectively) but not with shunt fraction (r = 0.14). Increased plasma glucagon concentration in cirrhosis is probably a result of diminished hepatic clearance. However, increased plasma concentration of glucagon does not appear to cause a hyperdynamic circulatory state or sodium retention.
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PMID:Plasma glucagon concentration in cirrhosis is related to liver function but not to portal-systemic shunting, systemic vascular resistance, or urinary sodium excretion. 198 11

The addition of glucose to the medium of Tetrahymena thermophila results in a 7-fold repression of galactokinase (EC 2.7.1.6; ATP:D-galactose-1-phosphotransferase). The presence of millimolar amounts of the catecholamines dopa, dopamine, norepinephrine, and epinephrine or the hormone glucagon also results in the repression of galactokinase in the absence of glucose. The addition of millimolar amounts of adrenergic agonists (isoproterenol, tyramine, 2-amino-6,7-dihydroxytetrahydronaphthalene) results in significant repression of galactokinase in the absence of glucose; concentrations of 2-amino-6,7-dihydroxytetrahydronaphthalene less than or equal to 10(-4) M result in a derepression of galactokinase specific activity. Addition of adrenergic antagonists (propranolol, dichloroisoproterenol) have no effect on galactokinase activity at concentrations less than 10(-4) M but do arrest cell growth at greater concentrations. The addition of the cAMP analogs caffeine or theophylline in millimolar amounts results in repression of galactokinase activity; however, cell growth is greatly slowed or completely arrested at these concentrations. Analysis of the repression response of several mutants demonstrates that mutants deficient in catecholamine biosynthesis are altered in their regulation of galactokinase. Measurements of intracellular cAMP levels for 0-24 h following the addition of several of the above compounds to exponentially growing cells did not demonstrate any change over this period. Measurement of intracellular cAMP levels for 24 h following the addition of glucose or galactose to exponentially growing wild-type and mutant cell strains did not demonstrate any difference in cAMP concentrations over this period although a wide range of galactokinase activity was exhibited. Starvation of wild-type cells prior to the addition of glucose in minimal medium without added carbohydrate resulted in a significant increase in cAMP following the addition of glucose. This increase is demonstrated to be dependent upon the ability of the cells to resume division after the arrest of growth and is not correlated with galactokinase regulation. These results support the conclusion that cAMP is not involved in the repression of galactokinase gene expression initiated by glucose or hormone-like effectors and demonstrate the participation of an adrenergic control system in galactokinase regulation which is subordinate to the regulation by glucose. A possible model is discussed.
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PMID:Regulation of galactokinase gene expression in Tetrahymena thermophila. I. Intracellular catecholamine control of galactokinase expression. 241 Apr 18

The extrahepatic diversion of essential splanchnic hepatotrophic factors may cause the liver atrophy and insufficiency that follows portacaval shunting. To investigate this, control dogs with end-to-side portacaval shunts (control-PCS, n = 6) were compared with dogs shunted 1 month after intraportal pancreatic islet autotransplantation (islet-Tx-PCS, n = 5). From the distal pancreas of each experimental dog, 1.95 +/- 0.49 X 10(5) islets were isolated by collagenase digestion and retransplanted within 3 hours. Assays of hepatocellular function (caffeine clearance) and hepatic blood flow (indocyanine green), conventional biochemical liver function tests, and glucose, insulin, and glucagon responses to intravenous glucose challenge were measured monthly and when dogs were killed. Four of six control-PCS dogs were killed 32 +/- 9 days after shunting because of more than 20% body weight loss; one control-PCS dog lost only 7% of body weight by day 56 and stabilized. No significant loss of body weight occurred in islet-Tx-PCS dogs (n = 5). Liver function test abnormalities seen in control-PCS dogs were absent in islet-Tx-PCS dogs. Both control-PCS and islet-Tx-PCS indocyanine green half-life measurements were significantly (p less than 0.05) prolonged at all times, indicating equally reduced hepatic blood flow after shunting for both groups. In contrast, islet-Tx-PCS caffeine half-life periods were significantly (p less than 0.05) shorter than in control-PCS dogs and were similar to those in normal dogs, indicating a protective effect of the transplanted islets on hepatocellular function. We conclude that intraportal pancreatic islet autotransplants prevent, by the local release of hepatotrophic factors within the liver, the metabolic abnormalities and loss of hepatic function after PCS.
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PMID:Hepatic insufficiency after portacaval shunting is prevented by prior intraportal pancreatic islet autotransplantation. 250

Caffeine has been reported to enhance performance by increasing fat utilization and by sparing liver and muscle glycogen. The lipolytic effect of caffeine has been reported to be diminished in response to previous carbohydrate loading of the subjects. The present study was designed to investigate the effects of caffeine during submaximal exercise in rats where the influence of dietary carbohydrate was removed by fasting. Rats were fasted overnight and given injection of 25 mg.kg-1 caffeine (CAF) or 0.9% NaCl (SAL) 60 min before exercise. They were run for 15, 30, and 60 min on a rodent treadmill up a 15% grade at 21 m.min-1. Plasma free fatty acids (FFA) were significantly elevated to 0.72 +/- 0.04 mM in CAF as compared to 0.45 +/- 0.03 mM in SAL at the beginning of exercise. During exercise, however, a significant difference in FFA levels between CAF and SAL was seen only at 30 min and not at other time points. No significant decrease in muscle glycogenolysis was observed in the CAF as compared to SAL rats, and the liver cyclic AMP remained the same in both CAF and SAL. Blood lactate (mM) showed an increase due to caffeine only at 15 min of exercise (CAF = 2.4 +/- 0.2; SAL = 1.7 +/- 0.3). Intravenous caffeine during exercise did not alter plasma glucagon or blood glucose. We conclude that caffeine has no effect on muscle glycogen utilization in fasted rats during exercise even though there was an increased FFA in CAF rats at the beginning of exercise.
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PMID:Effect of intravenous caffeine on muscle glycogenolysis in fasted exercising rats. 254 Mar 93

The endocrinological and biochemical mechanisms controlling energy expenditure in brown adipose tissue at the cellular as well as at the total tissue levels are briefly reviewed. Thermogenesis in brown adipose tissue is principally controlled by the activity of hormone-sensitive lipases that represent the 'flux-generating' step in the stimulus-calorigenesis sequence. Long chain fatty acids are the physiological messengers regulating mitochondrial respiration. Agents stimulating brown adipocyte lipolysis (catecholamines, glucagon, methylxanthines) also stimulate respiration, and conversely, agents inhibiting lipolysis (adrenergic antagonists, insulin, prostaglandins) also inhibit respiration. This indicates that lipolysis and respiration are functionally coupled in brown adipose tissue. On the other hand, brown adipose tissue thermogenic capacity increases during cold acclimation or adaptation to hyperphagia. Brown adipocyte proliferation and differentiation from precursor cells (interstitial cells and brown preadipocytes) represent the fundamental phenomena explaining the increase capacity of cold acclimated and/or hyperphagic animals for responding calorigenically to catecholamines. Physiological situations associated with a stimulation of energy expenditure and a negative energy balance (cold acclimation, exercise training, caffeine consumption) generally induce a stimulation of adipocyte proliferation in brown adipose tissue that is accompanied by a simultaneous inhibition of cell proliferation in white adipose tissue. The physiological significance of these metabolic adaptations is to modulate the capacity of homeothermic animals for energy expenditure in accordance with energy requirements.
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PMID:Regulation of energy expenditure in brown adipose tissue. 299 14

Neither insulin nor epinephrine influenced the incorporation of glucose into the acid-soluble or acid-insoluble glycogen pool of mouse embryos at the morula-early blastocyst stage during 5 h culture in the presence of radiolabelled glucose. During a 5 h chase culture of pulse-labelled embryos at this stage of development, acid-soluble glycogen labelled during the pulse was not utilized by the embryo but acid-insoluble glycogen was reduced. Addition of glucagon, insulin, epinephrine, cAMP, theophylline or caffeine during chase culture had no effect on the turnover of label in the glycogen pools of the embryo. These results indicate that the turnover of embryonic glycogen observed in vivo is not due to the direct effect of the hormones that regulate glycogen metabolism in the mother. Insulin was found to stimulate incorporation of glucose into non-glycogen macromolecules during both pulse and chase culture. Thus, whilst an effect of insulin on glycogen metabolism was absent, the anabolic effects of this hormone appear to have been expressed in the embryo at this stage of development.
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PMID:Metabolism of glucose by preimplantation mouse embryos in the presence of glucagon, insulin, epinephrine, cAMP, theophylline and caffeine. 301 Sep 22


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