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)

Eight men were studied during graded (47, 77, and 100% of maximal oxygen uptake) and prolonged (76%) exhaustive treadmill running. During graded exercise the glucagon concentration increased 35% from 81 plus or minus 7 pg/ml (mean and SE) at rest to 109 plus or minus 17 after the heaviest load. During prolonged exercise glucagon increased progressively to three times (226 plus or minus 40) the resting value. Norepinephrine increased from 0.40 plus or minus 0.06 ng/ml to 2.22 plus or minus 0.39, epinephrine from 0.07 plus or minus 0.01 to 0.42 plus or minus 0.13 during graded, and to 1.51 plus or minus 0.08 and 0.33 plus or minus 0.04, respectively, during prolonged exercise. Insulin concentrations were depressed during work except for the heaviest load. Fatty acids rose throughout prolonged exercise, whereas blood glucose significantly diminished 30 min afterward. Glucagon concentrations correlated significantly with norepinephrine and epinephrine concentrations during prolonged and with epinephrine during graded exercise. Although increments in catecholamines were similar, the glucagon secretion was larger during prolonged than during graded exercise. While increments in catecholamines might explain increased glucagon secretion during graded exercise, they cannot account completely for the rise of glucagon during prolonged exercise.
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PMID:Glucagon and plasma catecholamine responses to graded and prolonged exercise in man. 111 Feb 46

The influence of exercise on leg and splanchnic exchange of substrates was examined in eight insulin-dependent diabetics 24 h after withdrawal of insulin and in eight healthy controls studied at rest and after 40 min of bicycle ergometer exercise at 55-60% of maximal capacity. In four of the diabetic subjects, basal arterial ketone acid levels were 3-4 mmol/ liter (ketotic diabetics) and in the remainder, below 1 mmol/liter (nonketotic diabetics). ,ree fatty acid (FFA) turnover and regional exchange were evaluated with 14-C- labeled oleic acid. Leg uptake of blood glucose rose 13-18 fold during exercise in both the diabetics and controls and accounted for a similar proportion of the total oxygen uptake by leg muscles (25-28%) in the two groups. In contrast, leg uptake of FFA corresponded to 39% of leg oxygen consumption in the diabetic group but only 27% in controls. Systemic turnover of oleic acid was similar in the two groups. Splanchnic glucose output increased during exercise 3-4 fold above resting levels in both groups. In the diabetics, splanchnic uptake of lactate, pyruvate, glycerol, and glycogenic amino acids rose more than twofold above resting levels and was fourfold greater than in exercising controls. Total precursor uptake could account for 30% of the splanchnic glucose output in the diabetic group. In contrast, in the controls, total splanchnic uptake of glucose precursors was no greater during exercise than in the resting state and could account for no more than 11% of splanchnic glucose output. The augmented precursor uptake during exercise in the diabetics was a consequence of increased splanchnic fractional extraction as well as increased peripheral production of gluconeogenic substrates. The arterial glucagon concentration was unchanged by exercise in both groups, but was higher in the diabetics. In the diabetic subjects with ketosis in the resting state, exercise elicited a rise in arterial glucose and FFA, an augmented splanchnic uptake of FFA, and a 2-3 fold increase in splanchnic output of 3-hydroxybutyrate. Uptake of 3-hydroxybutyrate by the exercising leg rose more rapidly than splanchnic production, resulting in a fall in arterial levels of 3-hydroxybutyrate. It is concluded that (a) glucose uptake by exercising muscle in hyperglycemic diabetics is no different from that of controls; (b) splanchnic glucose output rises during exercise to a similar extent in diabetics and controls, while uptake of gluconeogenic substrates is markedly higher in diabetics and accounts for a greater proportion of total splanchnic glucose output; (c) exercise in diabetic patients with mild ketosis is associated with a rise in blood glucose and FFA levels as well as augmented splanchnic production and peripheral uptake of ketone bodies.
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PMID:Splanchnic and leg exchange of glucose, amino acids, and free fatty acids during exercise in diabetes mellitus. 113 76

The vasoactive effects of cholecystokinin-octapeptide (CCK-OP), pentagastrin, synthetic secretin, glucagon, and acetylcholine were assessed in the intestinal circulation of the dog. In pharmacologic doses of glucagon, CCK-OP, and, to a lesser degree, pentagastrin significantly increased blood flow and oxygen consumption. Atropine blocked the vasodilator effects of CCK-OP, pentagastrin, and acetylcholine but did not block those of glucagon. Neither the alpha-adrenergic blocker, phenoxybenzamine, nor the beta-adrenergic blocker, propranolol, blocked the vasodilator response to pentagastrin. Synthetic secretin had no significant effect on either blood flow or oxygen consumption in the intestinal segment. The vasodilator response to CCK-OP and pentagastrin appears to be mediated specifically through cholinergic receptors.
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PMID:Pharmacologic effects of gastrointestinal hormones on intestinal oxygen consumption and blood flow. 116 16

The systemic and coronary hemodynamic effects of 10, 20, 40 and 80 mug/kg glucagon have been studied in 9 anesthetized normoventilated closed-chest dogs. Intravenous administration of this agent produced a dose-related increase in the average coronary blood flow between 19% (10 mug/kg) and 49% (80 mug/kg). Coronary vascular resistance decreased by between 16% (10 mug/kg) and 39% (80 mug/kg). A--V O2 difference 1 min after the administration of glucagon no changes in myocardial oxygen extraction were observed after 5, 10 and 20 min. The calculated myocardial oxygen consumption rose up to 50% after 80 mug/kg glucagon. We conclude that the increase in coronary blood flow and the decrease in coronary resistance are mainly secondary to the metabolic effects of the increased myocardial contractility and heart rate, and that there is only an initial direct vasodilating effect on the coronary vessels.
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PMID:[Effects of glucagon on systemic circulation, coronary blood flow and myocardial oxygen consumption in the anesthetized dog (author's transl)]. 124 61

Periportal and perivenous hepatocytes possess different amounts and activities of the rate-generating enzymes of carbohydrate and oxidative energy metabolism and thus different metabolic capacities. This is the basis of the model of metabolic zonation, according to which periportal cells catalyze predominantly the oxidative catabolism of fatty and amino acids as well as glucose release and glycogen formation via gluconeogenesis, and perivenous cells carry out preferentially glucose uptake for glycogen synthesis and glycolysis coupled to liponeogenesis. The input of humoral and nervous signals into the periportal and perivenous zones is different; gradients of oxygen, substrates and products, hormones and mediators and nerve densities exist which are important not only for the short-term regulation of carbohydrate metabolism but also for the long-term regulation of zonal gene expression. The specialization of periportal and perivenous hepatocytes in carbohydrate metabolism has been well characterized. In vivo evidence is provided by the complex metabolic situation termed the 'glucose paradox' and by zonal flux differences calculated on the basis of the distribution of enzymes and metabolites. In vitro evidence is given by the different flux rates determined with classical invasive techniques, e.g. in periportal-like and perivenous-like hepatocytes in cell culture, in periportal- and perivenous-enriched hepatocyte populations and in perfused livers during orthograde and retrograde flow, as well as with noninvasive techniques using miniature oxygen electrodes, e.g. in livers perfused in either direction. Differences of opinion in the interpretation of studies with invasive and noninvasive techniques by the authors are discussed. The declining gradient in oxygen concentrations, the decreasing glucagon/insulin ratio and the different innervation could be important factors in the zonal expression of the genes of carbohydrate-metabolizing enzymes. While it is clear that the hepatocytes sense the glucagon/insulin gradients via the respective hormone receptors, it is not known how they sense different oxygen tensions; the O2 sensor may be an oxygen-binding heme protein. The zonal separation of glucose release and uptake appears to be important for the liver to operate as a 'glucostat'. Thus, zonation of carbohydrate metabolism develops gradually during the first weeks of life, in part before and in part with weaning, when (in rat and mouse) the fat- and protein-rich but carbohydrate-poor nutrition via milk is replaced by carbohydrate-rich food. Similarly, zonation of carbohydrate metabolism adapts to longer lasting alterations in the need of a 'glucostat', such as starvation, diabetes, portocaval anastomoses or partial hepatectomy.
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PMID:Hepatocyte heterogeneity in the metabolism of carbohydrates. 128 81

The dynamic model developed in our previous publications [1,2] was used to calculate the flux control coefficients of oxidation, phosphorylation and proton leak fluxes for isolated mitochondria and for three modes of work of intact cells (hepatocytes). The results obtained were compared with experimental data, especially those measured in the frame of the 'top-down approach' of the metabolic control theory. A good agreement for mitochondria and for intact cells was found. The control of the oxygen consumption flux is shared between the ATP utilization (main controlling factor), substrate dehydrogenation, proton leak and, in some conditions, the ATP/ADP carrier. The phosphorylation subsystem seemed to be controlled mainly by itself, while the proton leak was influenced by all three subsystems. It was also shown that the large relative change in the enzyme activity during inhibitor titration of mitochondria or cells could lead to the overestimation of some flux control coefficient values in experimental measurements. An influence of some hormones (glucagon, vasopressin, adrenaline and others) on the mitochondrial respiration was also simulated. Our results suggest that these hormones stimulate the substrate dehydrogenation as well as the phosphorylation system (ATP usage and, possibly, the ATP/ADP carrier).
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PMID:Theoretical studies on the control of the oxidative phosphorylation system. 132 30

In patients with cirrhosis the renal response to amino acid infusion is controversial. In addition, the renal and systemic metabolic effects of amino acids are unknown. Therefore, the present study examined the effects of amino acids on renal hemodynamics, renal and systemic oxygen (O2) consumption, and hormones in patients with cirrhosis. Twelve patients received an 8% amino acid solution for 30 minutes at a rate providing 250 mg of amino acids/kg body wt. Renal blood flow increased by 45% (P less than 0.05) and the glomerular filtration rate by only 9% (P greater than 0.05). Renal vascular resistance decreased by 23% (P less than 0.05), and renal perfusion pressure did not change significantly. Renal and systemic O2 consumption and pulmonary artery plasma glucagon level significantly increased. There were no significant changes in plasma osmolality, plasma volume, and plasma atrial natriuretic peptide concentrations. In conclusion, the results show that amino acid-induced renal vasodilation caused hyperperfusion but not renal hyperfiltration in patients with cirrhosis. In addition, renal hyperemia was associated with renal and systemic hypermetabolism.
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PMID:Hemodynamic, neurohumoral, and metabolic responses to amino acid infusion in patients with cirrhosis. 850 Jul 52

In order to test the degree of 'arterialization' and the occurrence of arterio- (or capillary-) venous differences in glucose concentrations for commonly used blood sampling sites (including the retrogradely cannulated dorsal hand vein with application of dry heat to this hand/arm--the 'heated-hand-technique'), oxygen partial pressure (oxygen saturation) and plasma glucose was determined in blood drawn from different venous sites before and after an oral glucose load (75 g). Experiments with and without heating (hot air 68 degrees C) were compared in nine healthy volunteers. Basal pO2 (and oxygen saturation) increased in the order cubital fossa vein less than superficial forearm vein less than dorsal hand vein. Heating raised pO2 by approximately 20 mmHg; P = 0.008) and oxygen saturation (P = 0.008-0.02) at all sites, including those on the contralateral arm. Capillary-venous glucose differences after the glucose challenge were significantly related to the sampling site (P less than 0.0001). They were reduced by approximately 50% in response to heat exposure (P = 0.008-0.011) and could be correlated to pO2-values (r = 0.92; P = 0.01). The lowest capillary-venous glucose concentration difference was measured with the 'heated-hand-technique' (0.4 +/- 0.1 mmol l-1). Heating did not alter integrated incremental glucose (capillary values), insulin, and C-peptide-responses and late, counter-regulatory responses (120-240 min after glucose) of cortisol, growth hormone, and adrenalin. However, the late glucagon response was enhanced (P = 0.011) by heating, concomitant with a significantly reduced 'reactive' decrement in glucose concentrations. In conclusion, the 'heated-hand-technique' provides blood more similar to arterial blood that can be obtained from other venous sampling sites. However, significant residual differences in pO2 and glucose concentrations remain. In addition, altered counter-regulatory hormone responses may occur with heating.
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PMID:Critical evaluation of the 'heated-hand-technique' for obtaining 'arterialized' venous blood: incomplete arterialization and alterations in glucagon responses. 139 46

The glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK) gene is modulated by oxygen. It was proposed that heme proteins might function as O2 sensors; their actions are impaired after replacement of the central Fe2+ ion by Co2+ and inhibition of heme synthesis by succinylacetone (SA). Therefore, the effects of CoCl2 and SA, alone and in combination, on the glucagon-dependent induction of PCK activity and PCK mRNA were investigated at different physiological oxygen tensions in primary rat hepatocyte cultures. The cells were exposed to 50 microM CoCl2 and/or 2 mM SA from 4-24 h. After addition of fresh media without CoCl2 or SA, PCK was induced with 1 nM glucagon. PCK activity and PCK mRNA were elevated to 100% at 16% O2 and to about 65% at 8% O2. CoCl2 reduced these increases to about 45% at 16% O2 and to about 35% at 8% O2. SA lowered the inductions to about 50% and 40% each at 16% and 8% O2. CoCl2 plus SA diminished the elevations to about 5% at both oxygen tensions. In the presence of CoCl2 and/or SA, ornithine decarboxylase induction by insulin was not impaired; lactate dehydrogenase did not leak from the cells, which in electron microscopical inspections had normal cell structures. These findings support the hypothesis that a heme protein is involved in the activation of the PCK gene and that it acts as an O2 sensor.
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PMID:Modulation of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene by oxygen in rat hepatocyte cultures. Evidence for a heme protein as oxygen sensor. 139 23

1) In isolated perfused rat liver, 14CO2 production from [1-14C]alpha-ketoisocaproate or [1-14C]glycine as well as ketogenesis from alpha-ketoisocaproate were stimulated upon exposure to hypoosmotic perfusion media, whereas hyperosmotic exposure inhibited. The effects of anisotonicity were preserved when ketogenesis from alpha-ketoisocaproate and 14CO2 production from [1-14C]glycine were already stimulated by glucagon. On the other hand, ketogenesis from tyrosine (2 mM) or octanoate (0.1 mM) were almost unaffected by anisoosmotic exposure. 2) With all ketogenic substrates studied, hypoosmotic (hyperosmotic) cell swelling (shrinkage) decreased (increased) the beta-hydroxybutyrate/acetoacetate ratio in effluent perfusate. A shift of the mitochondrial and cytosolic NADH systems to a more oxidized (reduced) state following hypoosmotic (hyperosmotic) exposure was also found upon infusion of beta-hydroxybutyrate/acetoacetate and lactate/pyruvate as redox indicator metabolite couples. The effects of anisotonicity on the beta-hydroxybutyrate/acetoacetate ratio were reversible upon normoosmotic reexposure and persisted throughout anisoosmotic exposure despite completion of volume regulatory K+ fluxes within 10-15 min. Hepatic oxygen consumption decreased by about 10% during hyperosmotic cell shrinkage and was transiently stimulated during hypoosmotic exposure. 3) There was a close relationship between ketogenesis from alpha-ketoisocaproate (0.5 mM) and the mitochondrial redox state, as assessed by the beta-hydroxybutyrate/acetoacetate ratio in effluent, regardless of whether the pathway was modulated by anisotonicity or glucagon. 4) Isoosmotic cell swelling induced by addition of glutamine (3 mM) was without significant effect on ketogenesis from octanoate and stimulated ketogenesis and 14CO2production from [1-14C]alpha-ketoisocaproate only slightly (i.e. by less than 10%); however, in each case the hydroxybutyrate/acetoacetate ratio in effluent perfusate decreased by about 20% upon addition of glutamine. 5) Stimulation of 14CO2production from [1-14C]glycine by hypoosmotic exposure and glucagon was only slightly affected when the accompanying decrease of the beta-hydroxybutyrate/acetoacetate ratio was reversed by addition of beta-hydroxybutyrate. 6) The data are compatible with a hypotonicity (hypertonicity)-induced shift of the mitochondrial NADH system to a more oxidized (reduced) state, probably due to a alterations of respiration. Mitochondrial swelling probably also occurs under the influence of glutamine. Modulation of ketogenesis from alpha-ketoisocaproate, but not of glycine oxidation by anisoosmotic exposure and glucagon can be related to the accompanying redox shifts. The observations support the concept that cell volume may be an important parameter determining liver cell function.
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PMID:Anisoosmostic liver perfusion: redox shifts and modulation of alpha-ketoisocaproate and glycine metabolism. 141 86


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