Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenylalanine hydroxylase activities in extracts of livers from rats pretreated with glucagon are higher than in controls. This time-dependent activation is seen when the hydroxylase is assayed in the presence of tetrahydrobiopterin, but not in the presence of 2-amino-4-hydroxy-6,7-dimethyltetrahydropterin. A maximum 4-fold stimulation of hydroxylase activity was correlated with a conversion of the multiple forms of the enzyme to a single form. This form is characterized by an increased extent of phosphorylation compared to the unactivated enzyme. Incorporation of radioactive inorganic phosphate into phenylalanine hydroxylase following administration of glucagon was determined after specific immunoprecipitation of the enzyme from partially purified preparations. Sodium dodecyl sulfate disc gel electrophoresis showed that stimulation of enzyme activity is accompanied by incorporation of 32Pi into the protein to the extent of 0.7 mol/mol of hydroxylase subunit. These results demonstrate the phosphorylation of hepatic phenylalanine hydroxylase in vivo and strongly support the idea that the activity of this enzyme can be hormonally regulated through a phosphorylation mechanism.
 ...
PMID:Glucagon stimulation of rat hepatic phenylalanine hydroxylase through phosphorylation in vivo. 69 Jan 16

The possible role of the hepatic fructose-6-phosphate substrate cycle (phosphofructokinase, fructose-1,6-diphosphatase) in the rapid hormonal regulation of gluconeogenesis was investigated in vivo in fasted normal and adrenalectomized rats after administration of [3-3H, U-14C]- or [3-3H, 6-14C]glucose. The plasma glucose 3H/14C ratio was used as an index of substrate cycling because the amount of 3H loss from liver hexose phosphates is determined by the extent of cycling. PFK and FDPase activities limit 3H loss during gluconeogenesis and glycolysis, respectively. Glucagon-stimulated hepatic glucose production is always accompanied by increased substrate cycling, i.e., increased FDPase and PFK activities. The high PFK activity may be a secondary event due possibly to elevated cellular fructose-6-phosphate levels. Decreased substrate cycling, i.e., lowered FDPase activity, always accompanies the depressed hepatic glucose production that occurs during hyperglycemia. Glucagon has no effect on substrate cycling in adrenalectomized rats that are insensitive to the hormone. The in vivo experiments presented provide evidence, although indirect, that glucagon administration results in changes in the fructose-6-phosphate substrate cycle in a living animal. Whether these changes are primary regulatory events or occur secondarily to hormone actions elsewhere is not known.
 ...
PMID:Fructose-6-phosphate substrate cycling and hormonal regulation of gluconeogenesis in vivo. 69 24

In unanesthetized normal and methylprednisolone (MP)-treated dogs the rate of appearance of glucose was measured simultaneously with 2-3H (RA2 = hepatic glucose output), 6-3H (Ra6 = hepatic glucose production), and 14C-glucose (U) (RaC) as tracers (primed constant rate infusion). The substrate ("futile") cycle of glucose (SC: gl in equilibrium gl-6-P) was obtained from Ra2 - Ra6, and Ra6 -RaC gave the recycling (RC) of radiocarbons. In normal dogs SC and RC represented 13% and 11% of Ra6, respectively. MP increased SC almost eightfold without altering RC. Infusion of glucagon (increased breakdown of glycogen, inhibition of glycogen synthetase) or mannoheptulose (inhibition of glucokinase) as well as exercise increased SC. MP greatly potentiated the effect causing SC to rise to 20 times the normal baseline. In both groups there was a direct correlation between Ra6 and SC. Glucose infusion did not alter SC in the controls, but increased it in the MP-treated dogs by suppressing Ra6 more than Ra2. It is suggested that the multifunctional character of gl-6-Pase is at least partly responsible for the glucose substrate cycle, using gl-6-P as one of the phosphate donors: gl-6-P + 3H-gl in equilibrium 3H-gl-6-P+gl. The activity of this enzyme is greatly elevated by the glucocorticoid, and it can be further enhanced by increasing the availability of gl-6-P by raising Ra6.
 ...
PMID:Studies on hepatic glucose cycles in normal and methylprednisolone-treated dogs. 83 49

Chloralose-anaesthesized dogs, starved for 24 hours, were used to determine the effects of 10 microgram/kg glucagon, administered i.v. as a single bolus injection, on liver substrates in situ (glycogen, glucose-1-phosphate, glucose-6-phosphate, glucose, fructose-6-phosphate, fructose-1,6-diphosphate, triose phosphates, glycerol-3-phosphate, phosphoenolypyruvate, pyruvate, lactate, citrate, malate, ATP, ADP, and AMP). liver samples were obtained by instant deep-freezing with Wollenberger clamps on four consecutive occasions at 10-minute intervals. Heart rate and blood pressure were continuously monitored. Serial liver sampling per se had no significant effects on liver metabolism or systemic haemodynamics in a group of control animals. In a second group glucagon, administered after the initial freeze-clamp sampling to obtain baseline values, led to a marked activation of the glycogenolytic pathway resulting in glucose release from the liver.
 ...
PMID:Effects of glucagon on liver metabolism in intact dogs. 92 72

By measuring the specific radioactivity of glucose released from isolated perfused livers of normal, fed rats in the presence of [U-14C]fructose, the gluconeogenetic and glycogenolytic contributions to glucose production were estimated. After 20 min of perfusion with 4 mM fructose, glycogenolysis was inhibited by 40% in the absence and by 70% in the presence of glucagon (3 nM). Glucagon decreased the release of lactate plus pyruvate and enhanced glucose formation from fructose without affecting its uptake. Glycerol (4 mM) and xylitol (3 mM) had qualitatively similar, but smaller effects on glucagon-stimulated glycogenolysis. The glucagon-mediated phosphorylase b to a conversion was not altered by fructose, indicating that glycogenolysis was decreased as a consequence of an inhibition of phosphorylase a. During the first minutes after the addition of fructose, decreased ATP/AMP ratios and tissue Pi levels correlated with a transient increase of phosphorylase a activity. It was concluded that the effects of fructose on the control of hepatic glycogenolysis and glucose production were the result of a complex interplay between a transient b to a conversion of phosphorylase and an inhibition of the a-form of the enzyme, possibly by fructose 1-phosphate and other phosphorylated metabolites.
 ...
PMID:Interactions of glucagon and fructose in the control of glycogenolysis in perfused rat liver. 100 7

The effects of various nucleosides and nucleotides upon glucagon secretion from the isolated perfused rat pancreas were studied. Increasing glucagon secretion was found with increasing concentrations of exogenous cyclic AMP (2 X 10(-4) M, 2 X 10(-3) M and 1 X 10(-2) M). Stimulation of alpha cell secretion was also found with 2 X 10(-3) M 2'AMP, 3'AMP, 5'AMP, ADP, Adenosine, NADP, and NADPH. One X 10(-3) M cyclic GMP elicited significant glucagon secretion. The pattern of glucagon release was similar in all cases with peak secretion occurring during the 30- to 90-s time period following initiation of the stimulus. No significant increase of glucagon secretion was found in response to ATP, guanosine, 2'GMP, 3'GMP, 5'GMP, GTP, xanthosine, inosine, adenine, xanthine, thymidine, cytidine, ribose, nicotinamide, and uric acid. On the basis of the above results, the structural requirement for stimulation of glucagon secretion appears to be adenine linked to ribose, with phosphate groups being unnecessary. The conclusion of this study is that a new class of compounds capable of stimulating glucagon secretion has been identified, and important questions are thus raised about the mechanism of the action of exogenous cyclic AMP.
 ...
PMID:Nucleotide and nucleoside stimulation of glucagon secretion. 110 53

The effects of insulin on the renal handling of sodium, potassium, calcium, and phosphate were studied in man while maintaining the blood glucose concentration at the fasting level by negative feedback servocontrol of a variable glucose infusion. In studies on six water-loaded normal subjects in a steady state of water diuresis, insulin was administered i.v. to raise the plasma insulin concentration to between 98 and 193 muU/ml and infused at a constant rate of 2 mU/kg body weight per min over a total period of 120 min. The blood glucose concentration was not significantly altered, and there was no change in the filtered load of glucose; glomerular filtration rate (CIN) and renal plasma flow (CPAH) were unchanged. Urinary sodium excretion (UNaV) decreased from 401 plus or minus 46 (SEM) to 213 plus or minus 18 mueq/min during insulin administration, the change becoming significant (P smaller than 0.02) within the 30-60 min collection period. Free water clearance (CH2O) increased from 10.6 plus or minus 0.6 to 13 plus or minus 0.5 ml/min (P smaller than 0.025); osmolar clearance decreased and urine flow was unchanged. There was no change in plasma aldosterone concentration, which was low throughout the studies, and a slight reduction was observed in plasma glucagon concentration. Urinary potassium (UKV) and phosphate (UPV) excretion were also both decreased during insulin administration; UKV decreased from 66 plus or minus 9 to 21 plus or minus 1 mueq/min (P smaller than 0.005), and tupv decreased from 504 plus or minus 93 to 230 plus or minus 43 mug/min (P smaller than 0.01). The change in UKV was associated with a significant reduction in plasma potassium concentration. There was also a statistically significant but small reduction in plasma phosphate concentration which was not considered sufficient alone to account for the large reduction in UPV. Urinary calcium excretion (UCaV) increased from 126 plus or minus 24 to 200 plus or minus 17 mug/min (P smaller than 0.01). These studies demonstrate a reduction in UNaV associated with insulin administration that occurs in the absence of changes in the filtered load of glucose, glomerular filtration rate, renal blood flow, and plasma aldosterone concentration. The effect of insulin on CH2O suggests that insulin's effect on sodium excretion is due to enhancement of sodium reabsorption in the diluting segment of the distal nephron.
 ...
PMID:The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. 112 Jul 86

Previous studies have shown that guanine nucleotides, acting at a site termed nucleotide regulatory site, are required for activation of hepatic adenylate cyclase and that glucagon facilitates this process. This study shows that only guanine nucleotides containing triphosphate groups at the 5' position of ribose (or 3'-deoxyribose) are capable of activating the enzyme. The terminal phosphate is not utilized in the activation process since 5'-guanylylimidodiphosphate (Gpp(NH)p and 5'-guanylyl methylenediphosphonate, analogues of GTP that are not utilized in transferase or hydrolase reactions, stimulate enzyme activity. The nucleotides bind in their free form at the regulatory site; chelation by magnesium ion shifts the apparent concentration dependence for activation by Gpp(nh)p. GDP inhibits competitively Gpp(NH)p-stimulated activity and inhibits basal activity and activities stimulated by glucagon. Activation of the enzyme by Gpp(NH)p is a slow process; the length of the lag time increases as an inverse function of nucleotide concentration and is as long as 4 min before onset of increased enzyme activity. Following pretreatment with Gpp(NH)p and extensive washing of hepatic membranes, the enzyme displays immediate increases in activity with rates that are a function of the nucleotide concentration during pretreatment; the rates remain constant for at least 6 min despite the absence of Gpp(NH)p in the medium. Studies with labeled Gpp(NH)p show that the intact nucleotide remains firmly bound to the membranes after extensive washing, suggesting that the persistence of adenylate cyclase activity may be related to slow dissociation of the nucleotide from the regulatory site. Addition of 1 nM glucagon, a submaximal concentration, does not abolish the lag phase of Gpp(NH)p activation even at saturating concentration of the nucleotide (1 muM or higher). The maximal steady state rate is achieved under these conditions. Addition of 2 muM glucagon, a saturating hormone concentration, does not alter the steady state rate but abolishes the lag phase of Gpp(NH)p activation. The transient kinetics of Gpp(NH)p activation and the effects of glucagon thereon are discussed in terms of a three state model in which the guanine nucleotide induces the formation of an intermediate transition state that displays no increase in enzyme activity over the basal state and which slowly isomerizes to a high activity state of the adenylate cyclase system; glucagon acts by accelerating the rate of isomerization.
 ...
PMID:The hepatic adenylate cyclase system. I. Evidence for transition states and structural requirements for guanine nucloetide activiation. 112 49

Glucagon and glucagon fragments from the carboxyl terminal end of the protein act at 0.01 to 0.1 mM concentrations on isolated rat liver mitochondria to sustain the rate of fixation of CO2 in the presence of pyruvate. The rate of decarboxylation of pyruvate is also increased by these substances. Similar effects are found with bacitracin, vanocomycin and cephalothin but not with any other of the proteins, peptides and antibiotics tested. The action of glucagon requires the presence of added magnesum ion. The addition of glucagon results in a better maintenance of adenosine triphosphate (ATP), and it leads to a greater degree of swelling of the mitochondria during the incubation. The effect of glucagon is partially mimicked by atractyloside, but it appears that glucagon is not exerting its effect by an atractyloside-like action. Added ATP obliterates the effect of added glucagon by sustaining fixation of CO2 However in incubations made in the presence of lower than usual levels of inorganic phosphate (2 mM vs. 8 mM) an effect of glucagon can be seen in the presence of ATP.
 ...
PMID:Effects of glucagon and other peptides on fixation of CO2 by rat liver mitochondria. 115 28

In control animals a 2-fold increase in liver phosphorylase activity 10min after adrenaline treatment was associated with a 55% increase in plasma glucose (P less than 0.001); at 20 min plasma glucose was 247% of the control value (P less than 0.001). Liver phosphorylase activity was decreased by 74%, 20 min after fructose injection (P less than 0.001), and, although phosphorylase activity increased 5-fold within 5 min of adrenaline injection, no increases in plasma glucose concentration over that found in fructose-injected animals which did not receive adrenaline occurred at either 5, 10 or 20 min. The data confirm inactivation of liver phosphorylase after fructose injection and suggest inhibition of the adrenaline-activated enzyme by the decrease in Pi and elevation of fructose 1-phosphate concentrations produced by the injection of fructose. These findings may be causally related to the hypoglycaemia and the lack of response to glucagon seen in patients with hereditary fructose intolerance after fructose ingestion.
 ...
PMID:Failure of adrenaline to induce hyperglycaemia after fructose injection in young mice. 115 94


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>