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)

Frog liver adenylate cyclase was characterized with respect to divalent cation interaction and hormonally stimulated activities. The enzyme catalyzed the synthesis of cyclic [32P]3',5'-AMP from alpha-32P-labeled ATP. The activity of the enzyme was linear with time and protein concentration. The Km for ATP was 0.5 mM, in the presence or absence of stimulators. The temperature optimum was 25 degrees. GTP (10(-4) M) increased the stimulation of adenylate cyclase by epinephrine. Similar activities were obtained using 5 mM Mg2+ or Mn2+. At higher concentrations, both ions inhibited epinephrine-stimulated, but not basal or fluoride-stimulated activities. Approximately equivalent hormonal stimulation was obtained with maximal stimulating concentrations of epinephrine, isoproterenol, glucagon, and prostaglandin E1. Norepinephrine was less stimulatory. Only catecholamine-stimulated activities were inhibited by propranolol (10(-5) M). The data suggest that catecholamines stimulate frog liver adenylate cyclase through interactions with beta adrenergic receptors. The adenylate cyclase in frog liver differs from its mammalian counterpart in its response to temperature and maximally stimulatory concentrations of hormones.
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PMID:Catecholamine and divalent cation effects on frog liver adenylate cyclase. 660 83

Membrane fractions obtained from hepatocytes treated with glucagon exhibited a decreased glucagon (with or without GTP)-stimulated adenylate cyclase activity. A maximum effect was seen in around 5 min. No change in the rate of cyclic AMP production was observed for the basal, NaF-, p[NH]ppG (guanosine 5'-[beta, gamma-imido]-triphosphate)- and GTP-stimulated states of the enzyme. The lag observed in the p[NH]ppG-stimulated adenylate cyclase activity of native membranes was abolished when membranes from glucagon-pretreated cells were used. When Mn2+ replaced Mg2+ in the assays, the magnitude of the apparent desensitization was decreased. Mn2+ abolished the lag of onset of p[NH]ppG-stimulated activity in native membranes. The desensitization process was dose-dependent on glucagon, which exhibited a Ka of 4 X 10(-10) M. Depletion of intracellular ATP did not affect this process. It is suggested that this desensitization occurs at the level of the guanine nucleotide-regulatory protein.
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PMID:Challenge of hepatocytes by glucagon triggers a rapid modulation of adenylate cyclase activity in isolated membranes. 661 75

Immunotitrations of rat liver hydroxymethylglutaryl-CoA (HOMeGlt-CoA) reductase activity were performed before and after short-term changes in the nutritional or hormonal state of the animals. Changes in enzyme activity (increase or decrease) within 1 h following cholesterol feeding or glucagon or mevalonolactone administration to normal rats, or insulin administration to diabetic rats were accompanied by no change in the specific activity of the enzyme, as determined from the quantity of enzyme activity inactivated by a fixed quantity of antibody. These results support the conclusion that the loss in enzyme activity was due to conversion of the enzyme to immuno-unreactive products. In agreement with this conclusion the enzyme activity lost after these short-term physiological changes was not restorable by phosphoprotein phosphatase action. On the other hand, incubation of rat liver microsomes with ATP and Mg2+ decreased the specific activity of HOMeGlt-CoA reductase about tenfold, as determined by immunotitration. The low specific activity produced under these conditions was increased by phosphatase action to nearly the original level. The above evidence suggests that the changes in HOMeGlt-CoA reductase activity that resulted from short-term physiological changes in hormonal or nutritional states of an animal were brought about by a change in the quantity of enzyme, and not by reversible phosphorylation of pre-existing enzyme.
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PMID:Regulation of short-term changes in hepatic beta-hydroxy-beta-methylglutaryl-CoA reductase activity. 711 48

In order to examine the effect of a single bout of exercise on hepatic mitochondrial function, starved untrained male rats swam at 34-35 degrees C with a tail weight (5% of body wt.) for 100 min. The rates of ADP-stimulated and uncoupled respiration were higher in the mitochondria isolated from the exercised rats regardless of the substrate utilized. Succinate-linked Ca2+ uptake was 48% greater in the exercised group; however, Ca2+ efflux was markedly depressed. The inhibition of Ca2+ uptake by Mg2+ was higher in the control group, so that the difference in Ca2+ uptake between the two groups was greater in the presence of Mg2+ than in its absence. The response of phosphorylating respiration and Ca2+ fluxes to exogenous phosphate and the pH of the assay medium differed in the exercise group. These observations with the exercised group were not related to non-specific stress. The exercise-induced mitochondrial-functional alterations are reminiscent of those obtained from mitochondria isolated from glucagon- or catecholamine-treated sedentary rats. Thus, adrenergic stimulation as well as other factors may be operating during exercise, leading to an alteration of mitochondrial function in vitro.
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PMID:Exercise-induced alterations of hepatic mitochondrial function. 716 27

Duodenal ulcer patients with normal (n = 36) or increased (n = 24) gastric acid production during maximal pentagastrin stimulation, were examined preoperatively and at different intervals (up to 1 year) after highly selective vagotomy (HSV). Fasting levels of gastrin, parathormone, calcitonin, proteins, calcium and magnesium fractions, inorganic phosphate and alkaline phosphatase were determined in serum, those of glucagon in plasma. Both types of patients have the same gastrin levels preoperatively (approx. 36 pg-equiv./ml). Magnesium and alkaline phosphatase are significantly higher in patients with a normal secretory response than in those with hypersecretion. The postoperative gastrin increase is significantly higher in the former than in the latter, while postoperative glucagon levels drop in both groups. The analysis of calcium fractions and the dissociation constant did not show any HSV-mediated change in calcium metabolism. The magnesium levels, however, are lower one year after the operation than in the pre-operative period in patients with normosecretion. In this group parathormone and calcitonin remain unchanged while in patients with a hypersecretory response a slight (parathormone) or moderate (calcitonin) tendency towards low values can be recognized in the post-operative period. We conclude that the duodenal ulcer patients probably belong to groups with different pathophysiological behaviour which do not have identical reactions to HSV. Imbalances in the metabolism of minerals and that of related hormones could not be demonstrated up to one year after HSV.
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PMID:Gastrinemia, serum minerals and calciotropic hormones following highly selective vagotomy in duodenal ulcer patients. Results of a 1-year study. 721 25

Previous work by this and other laboratories has shown that glucagon administration stimulates calcium uptake by subsequently isolated hepatic mitochondria. This stimulation of hepatic mitochondrial Ca2+ uptake by in vivo administration of glucagon was further characterized in the present report. Maximal stimulation of mitochondrial Ca2+ accumulation was achieved between 6-10 min after the intravenous injection of glucagon into intact rats. Under control conditions, Ca2+ uptake was inhibited by the presence of Mg2+ in the incubation medium. Glucagon treatment, however, appeared to obliterate the observed inhibition by Mg2+ of mitochondrial Ca2+ uptake. Kinetic experiments revealed the usual sigmoidicity associated with initial velocity curves for mitochondrial calcium uptake. Glucagon treatment did not alter this sigmoidal relationship. Glucagon treatment significantly increased the V max for Ca2+ uptake from 292 +/- 22 to 377 +/- 34 nmoles Ca2+/min per mg protein (n = 8) but did not affect the K 0.5, (6.5-8.6 microM). Since the major kinetic change in mitochondrial Ca2+ uptake evoked by glucagon is an increase in V max, the enhancement mechanism is likely to be an increase either in the number of active transport sites available to Ca2+ or in the rate of Ca2+ carrier movement across the mitochondrial membranes.
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PMID:The effect of glucagon on the kinetics of hepatic mitochondrial calcium uptake. 725 3

Rat liver plasma membrane phospholipid headgroups or fatty acids were modified by enzymatic transmethylation or transacylation. To evaluate the effect of phospholipid modification on adenylate cyclase (AC), one of the enzymes of phospholipid metabolism as well as AC were measured in the same incubation medium. Methyl transfer from S-adenosyl-L-methionine (SAM) to phosphatidylcholine (PC) was the highest at pH 9.2. At low concentrations of SAM, synthesis of PC as well as synthesis of the monomethyl derivative were considerably decreased and Mg2+ had no effect at pH 9.2 or at pH 6.5. When phospholipid methylation was increased in relation to SAM concentration, there was no change in basal, NaF- and glucagon-stimulated AC. Methylation was not modified when AC was stimulated. On the other hand, there was an increase in the basal, NaF- and glucagon-stimulated AC when linoleate was incorporated into the membrane phospholipids. Other unsaturated fatty acids had no effect. The synthesis of linoleoyl-PC from added lysophosphatidylcholine (LPC) also stimulated AC and this in turn partly prevented the inhibitory effect of LPC. Thus in isolated plasma membranes transmethylation has no direct effect on AC, whereas synthesis of linoleoyl molecular species can modulate AC in a way which does not depend on the membrane fluidity.
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PMID:Phospholipid modifications and adenylate cyclase in rat liver plasma membranes. 734 Apr 38

Isolated hepatocytes converted exogenous [alpha-32P]ATP to cyclic [32P]AMP at high rates. This system was used for kinetic studies of the effects of glucagon, fluoride, free magnesium and free ATP4- on adenylate cyclase. In the absence or presence of glucagon, free Mg2+ activated adenylate cyclase by decreasing the Km for MgATP2- without changing V. Free ATP4- was not a potent inhibitor of adenylate cyclase and the only effect of glucagon was to increase V. Fluoride also increased the V of adenylate cyclase, but, in contrast to the results obtained with glucagon, the effect increased as the concentration of free Mg2+ increased. One explanation of the effect of fluoride, consistent with the idea that free Mg2+ activates adenylate cyclase and free ATP is not an inhibitor, is that fluoride increases the affinity of the enzyme for Mg2+. Weak inhibition of adenylate cyclase by ATP4- in the presence of fluoride cannot be excluded.
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PMID:The adenylate cyclase activity of isolated hepatocytes actions of glucagon and sodium fluoride. 739 47

The G-protein-mediated coupling of a glucagon receptor to ATP-dependent K channels--KATP--has been studied in insulin-secreting cells using the patch clamp technique. In excised outside-out patches, KATP channel activity was inhibited by low concentrations of glucagon (IC50 = 2.4 nM); the inhibitory effect vanished at concentrations greater than 50 nM. In cell-attached patches, inhibition by bath-applied glucagon was seen most often, although stimulation was observed in a few cases. A dual action of the hormone is proposed to resolve these apparently divergent results. In excised inside-out patches, KATP channel activity was inhibited by addition of beta gamma subunits purified from either erythrocyte or retina (IC50 = 50 pM and 1 nM, respectively). Subsequent exposure of the patch to alpha i or alpha o reversed this effect. In excised inside-out patches, increasing Mg2+ in the bath stimulated the channel activity between 0 and 0.5 nM, but blocked it at higher concentrations (IC50 = 2.55 mM). In most cases (70%), GTP had a stimulatory effect at concentrations up to 100 microns. However, in three cases, similar GTP levels had clear inhibitory effects. In excised inside-out patches, cholera toxin (CTX) caused channel inhibition. Although the effect could not be reversed by removal of the toxin, the activity was restored by subsequent addition of purified alpha i or alpha o. These results are compatible with a model whereby channel inhibition by activated Gs-coupled receptors occurs, at least in part, via association of the beta gamma subunits of Gs with alpha i/alpha o subunits and deactivation of the alpha i/alpha o-dependent stimulatory pathway. On the basis of this hypothesis, a model is developed to describe the effects of G proteins on the KATP channel, as well as to account for the concentration-dependent stimulation and inhibition of KATP channel by Mg2+. An interpretation of the ability of glucagon to potentiate, but not initiate, insulin release is also given in terms of this model and the effects of ATP on KATP channels.
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PMID:Characterization of the G protein coupling of a glucagon receptor to the KATP channel in insulin-secreting cells. 770 64

We have investigated the mechanism of the rebound of glycogen stores in the liver of 72-h fasted rats. The liver of 72- and 96-h fasted rats contains significant amounts of glycogen (about 5 mg/g, wet weight) as compared to the liver of 24- and 48-h fasted rats, which contains less than 2 mg of glycogen/g of liver, wet weight. Rebound of glycogen does not involve glycogen synthase activation or glycogen phosphorylase inhibition. It could be dependent on the concentration of the precursor substrate of glycogenesis, i.e. glucose 6-phosphate (Glc-6-P), which is higher by about 45% in the liver of 72- and 96-h fasted rats than in the liver of 48-h fasted rats. The 72-h increase of Glc-6-P compared with the 48-h values could not be explained either by late modifications of the total activities of glucokinase, hexokinases, Glc-6-P dehydrogenase, and glucose-6-phosphatase (Glc-6-Pase) or by changes in plasma glucose and insulin/glucagon ratio. In agreement with the fact that total glucose output tends to decrease upon prolonged fasting, the increase of Glc-6-P concentration in the liver of 72-h fasted rats suggests the involvement of a metabolite inhibition of Glc-6-Pase. The increase of the alpha-ketoglutarate concentration in the 72- and 96-h fasted liver with regard to the 48-h fasted liver (about three times) might account for such an inhibition since we show here that Glc-6-Pase is inhibited in vitro in the presence of relevant concentrations of alpha-ketoglutarate, Glc-6-P, and Mg2+ ions.
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PMID:Investigation of the mechanism of glycogen rebound in the liver of 72-hour fasted rats. 820 76


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