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 increased fuel demands of the working muscle necessitate that metabolic processes within the liver be accelerated accordingly. The sum of changes in hepatic glycogenolysis and gluconeogenesis are closely coupled to the increase in glucose uptake by the working muscle, due to the actions of the pancreatic hormones. The exercise-induced rise in glucagon and fall in insulin interact to stimulate hepatic glycogenolysis, whereas the increase in gluconeogenesis is determined primarily by glucagon action. The increment in gluconeogenesis is caused by increases in hepatic gluconeogenic precursor delivery and fractional extraction as well as in the efficiency of intrahepatic conversion to glucose. Glucagon stimulates the latter two processes. Epinephrine may become important in the regulation of hepatic glucose production during prolonged or heavy exercise when its levels are particularly high. On the other hand, there is no evidence that hepatic innervation is essential for the rise in hepatic glucose production during exercise. Nonesterified fatty acid (NEFA) delivery to, uptake of, and oxidation by the liver are accelerated during prolonged exercise, resulting in an increase in ketogenesis. The rate of the first two of these processes is largely determined by factors that stimulate fat mobilization. The third step is regulated by both NEFA delivery to and glucagon-stimulated fat oxidation within the liver. The increase in hepatic fat oxidation produces energy that fuels gluconeogenesis. The shuttling of amino acids to the liver provides carbon-based compounds that are used for gluconeogenesis, transfers nitrogen to the liver, and supplies substrate for protein synthesis. During exercise, metabolic events within the liver, which are regulated by hormone levels and substrate supply, integrate pathways of carbohydrate, fat, and amino acid metabolism. These processes function to provide substrates for muscular energy metabolism and conserve carbon in glucose and nitrogen in protein.
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PMID:Hepatic fuel metabolism during muscular work: role and regulation. 205 58

To examine the impact of opiate blockade on glucose counterregulation we performed two hypoglycemic insulin clamp studies with and without naloxone in healthy subjects and well-controlled insulin-dependent (IDDM) patients with defective glucose counterregulation. During both studies plasma glucose fell to 55-60 mg/dl and was then maintained at that level using a variable glucose infusion. In normal subjects, naloxone increased glucose production, thereby reducing the exogenous glucose dose needed to maintain the hypoglycemic plateau. Epinephrine and cortisol responses to hypoglycemia were increased during naloxone plus insulin compared with insulin alone; glucagon responses were unaffected. IDDM patients with suppressed hepatic and hormonal responses to insulin-induced hypoglycemia also demonstrated greater stimulation of glucose production as well as epinephrine, growth hormone, and cortisol release during the naloxone study. In the absence of hypoglycemia, naloxone did not significantly affect glucose production or glucoregulatory hormones. We conclude that opiate blockade augments glucoregulatory responses to insulin-induced hypoglycemia, even in IDDM patients with preexisting defects in glucose counterregulation. This effect is at least in part due to enhanced counterregulatory hormone release during hypoglycemia. Endogenous opiates may modulate hormonal responses during hypoglycemia; their blockade could provide a means of ameliorating defective counterregulation in IDDM patients.
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PMID:Opiate blockade enhances hypoglycemic counterregulation in normal and insulin-dependent diabetic subjects. 205 61

Epinephrine caused hyperglycemia in part by increasing gluconeogenesis. However, the mechanism of its gluconeogenic effects has not been studied in ruminants. This study was undertaken to examine the effect of epinephrine on the net hepatic uptake of selected glucose precursors in sheep. The major abdominal blood vessels of the sheep were catheterized in normal and alloxan diabetic sheep. Glucose production, metabolic clearance of glucose, and the hepatic removal of certain glucose precursors were determined before, during, and after epinephrine infusion. Epinephrine increased the hepatic glucose output, the concentrations of lactate and glycerol in plasma, and the net hepatic uptake and fractional hepatic extraction of lactate and glycerol. These effects were independent of changes in the concentrations of insulin and glucagon in plasma. These results show that epinephrine directly stimulates hepatic gluconeogenesis in sheep.
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PMID:Effects of epinephrine on the net hepatic uptake of lactate, pyruvate, and glycerol in sheep. 205 10

1. The blood flow to the liver in fetuses near term, newborn and adult sheep was measured by the Fick principle, using radionuclide-labelled plastic microspheres, before and during infusion of adrenaline, noradrenaline or glucagon. 2. Glucose output and lactate consumption by the liver in sheep of each age group were calculated by application of the Fick principle using the concentration gradients of these metabolites measured in blood samples obtained, simultaneously with blood flow measurements, from catheters chronically implanted in the inflow and outflow vessels of the liver. 3. Catecholamines were infused into the portal vein of fetuses near term at a rate comparable with that at which they are known to be secreted in the sheep fetus during moderate to severe hypoxia. The cardiovascular and metabolic responses to these infusions were found to be comparable with those that occur in the fetus during hypoxia. 4. Catecholamines increased glucose output from the liver in all except the immediate post-partum animals. Catecholamines were less effective than glucagon in promoting glucose release. The mean increments in glucose output during adrenaline infusion were 0.055 +/- 0.015 mmol min-1 (100 g liver)-1 in the fetus, 0.122 +/- 0.024 mmol min-1 (100 g)-1 in the 2-week-old lambs, 0.078 +/- 0.019 mmol min-1 (100 g)-1 in young lambs and 0.049 +/- 0.012 mmol min-1 (100 g)-1 in the adult sheep. During glucagon infusion the mean glucose output increments were 0.146 +/- 0.023 mmol min-1 (100 g)-1 in the fetus, 0.274 +/- 0.085 mmol min-1 (100 g)-1 in the 2-week-old and young lambs and 0.180 +/- 0.054 mmol min-1 (100 g)-1 in the adult. Adrenaline was more potent than noradrenaline, suggesting that the major glycogenolytic response might be beta-receptor mediated. 5. In the immediate newborn period the output of glucose from the liver was high (0.20 +/- 0.05 mmol min-1 (100 g liver)-1 and was not statistically significantly increased by infusion either of glucagon or of catecholamines which resulted in similar increments of glucose output of about 0.128 +/- 0.133 mmol min-1 (100 g)-1. It is probable that the high output of glucose reflected the high endogenous circulating levels of catecholamines and glucagon in these animals at birth and that further infusions failed to add significantly to the already near-maximal glucose release.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Release of glucose from the liver of fetal and postnatal sheep by portal vein infusion of catecholamines or glucagon. 206 40

1. The inflow of Mn2+ across the plasma membranes of isolated hepatocytes was monitored by measuring the quenching of the fluorescence of intracellular quin2, by atomic absorption spectroscopy and by the uptake of 54Mn2+. The inflow of other divalent metal ions was measured using quin2. 2. Under ionic conditions which resembled those present in the cytoplasmic space, Mn2+, Zn2+, Co2+, Ni2+ and Cd2+ each quenched the fluorescence of a solution of Ca2(+)-quin2. 3. The addition of Mn2+, Zn2+, Co2+, Ni2+ or Cd2+ to cells loaded with quin2 caused a time-dependent decrease in the fluorescence of intracellular quin2. Plots of the rate of decrease in fluorescence as a function of the concentration of Mn2+ reached a plateau at 100 microM-Mn2+. 4. The rate of decrease in fluorescence induced by Mn2+ was stimulated by 20% in the presence of vasopressin. The effect of vasopressin was completely inhibited by 200 microM-verapamil. Adrenaline, angiotensin II and glucagon also stimulated the rate of decrease in the fluorescence of intracellular quin2 induced by Mn2+. 5. The rate of decrease in fluorescence induced by Zn2+, Co2+, Ni2+ or Cd2+ was stimulated by between 20 and 190% in the presence of vasopressin or angiotensin II. 6. The rates of uptake of Mn2+ measured by atomic absorption spectroscopy or by using 54Mn2+ were inhibited by about 20% by 1.3 mM-Ca2+o and stimulated by 30% by vasopressin. 7. Plots of Mn2+ uptake, measured by atomic absorption spectroscopy or with 54Mn2+, as a function of the extracellular concentration of Mn2+ were biphasic over the range 0.05-1.0 mM added Mn2+ and did not reach a plateau at 1.0 mM-Mn2+. 8. It is concluded that (i) hepatocytes possess both a basal and a receptor-activated divalent cation inflow system, each of which has a broad specificity for metal ions, and (ii) the receptor-activated divalent cation inflow system is the receptor-operated Ca2+ channel.
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PMID:The liver cell plasma membrane Ca2+ inflow systems exhibit a broad specificity for divalent metal ions. 216 60

Adrenaline-induced changes in heart rate, blood pressure, plasma adrenaline and noradrenaline, cortisol, glucagon, insulin, cAMP, glucose lactate, glycerol and beta-hydroxybutyrate were studied preoperatively and 4 and 24 h after skin incision in 8 patients undergoing elective cholecystectomy. Late postoperative responses of blood glucose, plasma cAMP, lactate and glycerol to adrenaline infusion were reduced, whereas other responses were unaffected. Blood glucose appearance and disappearance rate as assessed by [3H]3-glucose infusion was unchanged pre- and postoperatively. The increase in glucose appearance rate following adrenaline was similar pre- and postoperatively. These findings suggest that several beta-receptor-mediated responses to adrenaline are reduced after abdominal surgery.
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PMID:Endocrine, metabolic and cardiovascular responses to adrenaline after abdominal surgery. 217 Dec 89

To establish the role of hepatic nerves in hepatic glycogenolytic and gluconeogenic regulation during exercise, dogs underwent a laparotomy during which the hepatic nerves were either left intact (C; n = 8) or cut (DN; n = 5). At least 17 days after surgery, dogs were studied during 150 min of treadmill exercise (12% grade, 100 m/min). Glucose production (Ra) and gluconeogenesis (GNG) were assessed by combining [3-3H]glucose, [U-14C]alanine, and indocyanine green infusions with arterial, portal vein, and hepatic vein sampling. Glucagon and insulin were similar at rest and exercise in both groups. Norepinephrine rose from 145 +/- 10 to 242 +/- 32 pg/ml by 150 min of exercise in C and from 150 +/- 25 to 333 +/- 83 pg/ml in DN. Epinephrine rose from 66 +/- 7 pg/ml at rest to 108 +/- 10 and 148 +/- 24 pg/ml after 30 and 150 min of exercise in C and from 90 +/- 15 pg/ml at rest to 185 +/- 33 (P less than 0.05 compared with C) and 194 +/- 36 pg/ml after 30 and 150 min of exercise in DN. Plasma glucose fell gradually from 108 +/- 2 and 106 +/- 3 mg/dl at rest to 96 +/- 4 and 92 +/- 8 by the end of exercise in C and DN, respectively. Ra was similar in C and DN rising from 3.2 +/- 0.2 to 8.7 +/- 0.6 and 2.6 +/- 0.2 to 7.5 +/- 1.1 mg.kg-1.min-1, respectively, by the end of exercise. Minimum and maximum rates of GNG from alanine, glycerol, and lactate were elevated in DN compared with C during rest and exercise. However, the exercise-induced changes in GNG were similar in both groups. In conclusion, nerves to the liver are not essential to the increased Ra and glucose homeostasis during moderate-intensity exercise.
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PMID:Hepatic nerves are not essential to the increase in hepatic glucose production during muscular work. 220 Feb 75

We have studied the action of a series of vasoactive and antispasmodic agents on the intrahepatic vasoconstriction induced by adrenaline in the isolated perfused liver of rabbits. The arterial and portal venous resistance, oxygen consumption, liver weight and bile flow were investigated. The drugs used were as follows: nonspecific alpha-adrenergic antagonists (DH-ergocristine, dibenamine, phenoxybenzamine), vasodilators with a direct miscellaneous action (theophylline, papaverine, dipyridamole, glucagon, Aiu-cor by Instituto Gentilli, Italy [inosine, ATP, IPI, UTP]) and antispasmodics (piperylone, tropenziline, noraminophenazone). Adrenaline increased arterial and portal venous resistance followed by a diminution of oxygen consumption, liver weight and bile flow. alpha-Adrenergic antagonists inhibited the effects of adrenaline on portal venous resistance and oxygen consumption and especially the effects on hepatic arterial resistance. The most potent agent was phenoxybenzamine. In contrast to alpha-adrenoceptor blockade, the effects of other vasoactive agents were without a sustained influence on hepatic arterial resistance (excepting those of glucagon and dipyridamole). Some of them were effective as antagonists on responses in the portal venous bed (papaverine, Aiu-cor). Moreover, there were drugs exerting an enhancement of the vasoconstrictor responses of hepatic artery to low concentrations of adrenaline with no effect on the portal venous bed (piperylone, tropenziline). Theophylline and noraminophenazone exerted no effect either on the arterial or portal venous bed. No vasodilator agent antagonized the changes of the bile flow after adrenaline administration.
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PMID:A study of the inhibition of adrenaline-induced vasoconstriction in the isolated perfused liver of rabbit. 222 14

The cytoplasmic Ca2+ concentration ([Ca2+]i) was monitored in individual guinea-pig pancreatic alpha 2-cells exposed to modulators of glucagon release. Addition of the stimulatory amino acid arginine resulted in a sustained increase in [Ca2+]i, whereas the inhibitor glucose had the opposite effect. Epinephrine, the beta-adrenergic agonist isoproterenol, the adenylate cyclase activator forskolin and 8-bromo-cAMP transiently raised [Ca2+]i provided that the cells had been pretreated with glucose. However, simultaneous presence of glucose was not required and the effect occurred even in the absence of extracellular Ca2+. Carbachol, the alpha 2-adrenergic agonist clonidine and the sulfonylurea tolbutamide lacked effects on [Ca2+]i. In addition to providing support for the concept that glucagon release is positively modulated by [Ca2+]i, the results demonstrate that cAMP raises [Ca2+]i in the alpha 2-cells by mobilizing calcium incorporated in response to glucose.
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PMID:Cyclic AMP raises cytoplasmic calcium in pancreatic alpha 2-cells by mobilizing calcium incorporated in response to glucose. 255 Jan 36

The role of elevated plasma epinephrine concentrations in the regulation of plasma leucine kinetics and the contribution of beta-receptors were assessed in man. Epinephrine (50 ng/kg per min) was infused either alone or combined with propranolol (beta-blockade) into groups of six subjects fasted overnight; leucine flux, oxidation, and net plasma leucine forearm balance were determined during 180 min. Constant plasma insulin and glucagon concentrations were maintained in all studies by infusing somatostatin combined with insulin and glucagon replacements. Plasma leucine concentrations decreased from baseline during epinephrine infusion by 27 +/- 5 mumol/liter (P less than 0.02) due to a 22 +/- 6% decrease in leucine flux (P less than 0.05 vs. controls receiving saline) and to an increase in the metabolic clearance rate of leucine (P less than 0.02). Leucine oxidation decreased by 36 +/- 8% (P less than 0.01 vs. controls). beta-Blockade abolished the effect of epinephrine on leucine flux and oxidation. Net forearm release of leucine increased during epinephrine (P less than 0.01), suggesting increased muscle proteolysis; the fall of total body leucine flux was therefore due to diminished proteolysis in nonmuscle tissues, such as splanchnic organs. Nonoxidative leucine disappearance as a parameter of protein synthesis was not significantly influenced by epinephrine. Plasma glucose and FFA concentrations increased via beta-adrenergic mechanisms (P less than 0.001). The results suggest that elevation of plasma epinephrine concentrations similar to those observed in severe stress results in redistribution of body proteins and exerts a whole body protein-sparing effect; this may counteract catabolic effects of other hormones during severe stress.
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PMID:Elevation of plasma epinephrine concentrations inhibits proteolysis and leucine oxidation in man via beta-adrenergic mechanisms. 256 73


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