UNIPROT:P01275 - FACTA Search

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 maturation of Ca(2+) transport in mitochondria isolated from rat liver was examined, from 5 days before birth. The mitochondria used were isolated from liver homogenates by centrifugation at 22000g-min. Ca(2+) transport by mitochondria isolated from foetal liver is energy-dependent and Ruthenium Red-sensitive. The transmembrane pH gradient in these mitochondria is higher by about 7mV and the membrane potential lower by about 20mV than in adult mitochondria. The inclusion of 2mm-P(i) in the incubation medium enhances the protonmotive force by approx. 30mV. The rate of Ca(2+) influx in foetal mitochondria measured in buffered KCl plus succinate is low until about 2-3h after birth, when it increases to about 60% of adult values; approx. 24h later it has reached near-adult values. Higher rates of Ca(2+) influx are observed in the presence of 2mm-P(i); 3-5 days before birth the rates are about one-third of adult values and decline slightly as birth approaches. By 2-3h post partum they have reached adult values. The inclusion of 12.5mum-MgATP with the P(i) stimulates further the initial rate of Ca(2+) influx in foetal mitochondria. The rates observed are constant over the prenatal period examined and are 50-60% of those observed in adult mitochondria. Mitochondria isolated from foetal livers 4-5 days before birth retain the accumulated Ca(2+) for about 50min in the presence of 2mm-P(i). In the period 2 days before birth to birth, this ability is largely lost, but by 2-3h after birth Ca(2+) retention is similar to that of adult mitochondria. The presence of 12.5mum-MgATP progressively enhances the Ca(2+) retention time as development proceeds until 2-3h after birth, when it becomes less sensitive to added MgATP. Glucagon administration to older foetuses in utero enhances both the rate of mitochondrial Ca(2+) influx assayed in the presence of 2mm-P(i) and the time for which mitochondria retain accumulated Ca(2+) in the presence of 12.5mum-MgATP and 2mm-P(i). Its administration to neonatal animals leads to an increase in mitochondrial Ca(2+) retention similar to that seen in adult mitochondria. The data provide evidence that the Ruthenium Red-sensitive Ca(2+) transporter is potentially as active in foetal mitochondria 5 days before birth as it is in adult mitochondria. They also show that foetal mitochondria have an ability to retain accumulated Ca(2+) reminiscent of mitochondria from tumour cells and from hormone-challenged rat liver.
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PMID:Maturation in liver mitochondria of Ruthenium Red-sensitive calcium-ion-transport activity and the influence of glucagon administration in vivo and in utero. 617 Dec 66

To assess the effects of dialysis or hemofiltration on carbohydrate metabolism in uremia, we performed intravenous (IV) glucose tolerance tests (IV GTTs) after an overnight fast 48 hours following the last treatment in ten patients with chronic renal failure. Samples were obtained for plasma glucose, insulin, glucagon, and growth hormone levels throughout the GTTs in addition to basal samples for levels of plasma potassium and bicarbonate. The IV GTTs were performed at the end of a four-month period of standard hemodialysis (period 1) and then at the end of a four-month period of hemofiltration (period 2). Patients had mild glucose intolerance that did not change after hemofiltration, although the exaggerated insulin responses to glucose administration did significantly decrease in period 2. The fasting hyperglucagonemia did not decrease after hemofiltration but exhibited normal suppression with IV glucose. Levels of basal plasma bicarbonate and basal plasma potassium did not change significantly in period 2. Further studies investigating the beneficial metabolic effect of hemofiltration would seem to be indicated based on the data reported herein.
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PMID:Studies of carbohydrate metabolism after hemodialysis and hemofiltration in uremic patients. 704 44

It was hypothesized that the exercise-induced changes in glucoregulatory hormones and glucose production (Ra) occur as a result of a small deficit in glucose availability. To test this, 18-h fasted dogs performed 150 min of treadmill exercise with either the liver as the sole source of glucose (controls, n = 5) or with glucose infused from 0 to 50 min (period 1) and from 100 to 150 min (period 3) at rates designed to track the glucose utilization (Rd) response (ExoGlc, n = 5). The liver alone supplied glucose from 50 to 100 min (period 2). Isotopic and arteriovenous methods were used to assess Ra, Rd, and gluconeogenesis (GNG). Variable [3H]glucose infusion and frequent sampling were used to facilitate Ra measurements. Arterial glucose declined by -3.1 +/- 1.4, -4.3 +/- 2.9, and -6.4 +/- 3.7 mg/dl in periods 1-3 in controls (changes are mean values during each of the 50-min periods; P < 0.05). In ExoGlc, arterial glucose did not deviate from basal in periods 1 (+0.1 +/- 1.8 mg/dl) and 3 (+1.5 +/- 4.5 mg/dl) but fell from basal (P < 0.05) by the same amount as controls in period 2 (-5.7 +/- 2.1 mg/dl). Matching the Rd response with exogenous glucose led to increases in arterial and portal vein plasma insulin levels (P < 0.05) but did not affect glucagon, norepinephrine, epinephrine, and cortisol levels. Ra was elevated by 3.1 +/- 0.5, 4.0 +/- 1.1, and 4.7 +/- 1.1 mg.kg-1.min-1 in periods 1-3 in controls (P < 0.05). In ExoGlc, Ra rose by 0.0 +/- 0.4, 4.1 +/- 1.4 (P < 0.05), and 0.4 +/- 0.7 mg.kg-1.min-1, respectively, in periods 1-3. The rise in Ra was reduced in periods 1 and 3 of ExoGlc compared with controls (P < 0.02). GNG rose to approximately 250% basal in controls and did not respond with any significant difference in ExoGlc. In summary, the exercise-induced increases in counterregulatory hormones and GNG are present even when a deficit in glucose supply is eliminated by an exogenous glucose infusion. In contrast, the fall in insulin and the rise in hepatic glycogenolysis are greatly attenuated. The regulatory components affected by exogenous glucose predominate at the liver as deviations in plasma glucose of approximately 4% correspond to approximately 60% changes in Ra.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sensitivity of exercise-induced increase in hepatic glucose production to glucose supply and demand. 794 21

Two groups of conscious dogs were studied using isotopic tracer techniques to test the hypothesis that tumor necrosis factor (TNF) affects glucose production, lipolysis, amino acid, and protein kinetics. [1-13C]leucine, [15N2]urea, [6,6-2H2]glucose, and [2H5]glycerol were infused to determine the leucine, urea, glucose, and lipid kinetics, and NaH14CO3 was infused to determine the rate of CO2 production. In one group, after a 2-h basal period (period 1), recombinant human TNF was infused (prime, 2.5 micrograms/kg; constant, 62.5 ng.kg-1.min-1) for 2 h (period 2; group 1, n = 15). Group 2 received saline rather than TNF in period 2 (n = 3). TNF infusion caused a significant increase in endogenous glucose production, a significant increase in glucose clearance rate, and a decrease in glycerol flux. Although TNF infusion did not change leucine flux, leucine oxidation increased by 49% (P < 0.0001), and nonoxidative leucine disappearance decreased during TNF infusion by 13% (P < 0.0001). TNF infusion also caused a significant increase (18%) in endogenous urea production. TNF significantly increased plasma glucagon concentration. We conclude that TNF causes a shift toward carbohydrate metabolism and stimulates the oxidation of amino acids. Whereas whole body protein breakdown is not affected by TNF, protein synthesis is impaired, leading to an increase in net protein breakdown.
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PMID:Effect of tumor necrosis factor on substrate and amino acid kinetics in conscious dogs. 802 25

To investigate the temporal response of the liver to insulin and portal glucose delivery, somatostatin was infused into four groups of 42-h-fasted, conscious dogs (n = 6/group), basal insulin and glucagon were replaced intraportally, and hyperglycemia was created via a peripheral glucose infusion for 90 min (period 1). This was followed by a 240-min experimental period (period 2) in which hyperglycemia was matched to period 1 and either no changes were made (CON), a fourfold rise in insulin was created (INS), a portion of the glucose (22.4 mumol.kg-1.min-1) was infused via the portal vein (Po), or a fourfold rise in insulin was created in combination with portal glucose infusion (INSPo). Arterial insulin levels were similar in all groups during period 1 (approximately 45 pM) and were 45 +/- 9, 154 +/- 20, 43 +/- 7, and 128 +/- 14 pM during period 2 in CON, INS, Po, and INSPo, respectively. The hepatic glucose load was similar between periods and among groups (approximately 278 mumol.kg-1.min-1). Net hepatic glucose output was similar among groups during period 1 (approximately 0.1 mumol.kg-1.min-1) and did not change significantly in CON during period 2. In INS net hepatic glucose uptake (NHGU; mumol.kg-1.min-1) was -3.8 +/- 3.3 at 15 min of period 2 and did not reach a maximum (-15.9 +/- 6.6) until 90 min. In contrast, NHGU reached a maximum of -13.0 +/- 3.7 in Po after only 15 min of period 2. In INSPo, NHGU reached a maximum (-23.6 +/- 3.5) at 60 min. Liver glycogen accumulation during period 2 was 21 +/- 10, 84 +/- 17, 65 +/- 16, and 134 +/- 17 mumol/gram in CON, INS, Po, and INSPo, respectively. The increment (period 1 to period 2) in the active form of liver glycogen synthase was 0.7 +/- 0.4, 6.5 +/- 1.2, 2.8 +/- 1.0, and 8.5 +/- 1.3% in CON, INS, Po, and INSPo, respectively. Thus, in contrast to insulin, the portal signal rapidly activates NHGU. In addition, the portal signal independent of a rise in insulin, can cause glycogen accumulation in the liver.
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PMID:Comparison of the time courses of insulin and the portal signal on hepatic glucose and glycogen metabolism in the conscious dog. 855 Aug 54

We tested the hypothesis that the metabolic changes in glucose, lipid, and protein metabolism seen during tumor necrosis factor (TNF) infusion were due to the increase in plasma glucagon concentration rather than to the direct effects of TNF. We employed a pancreatic clamp technique to keep plasma insulin and glucagon concentrations constant throughout a 4-h isotope infusion. Glucose, lipid, and protein kinetics were measured by means of the primed, constant infusion of [6,6-2H]glucose, [2H5]glycerol, [2H2]palmitic acid, and [1-13C]leucine. After a 2-h baseline period (period 1), TNF was infused as a primed, constant infusion (prime, 2.5 micrograms/kg; constant infusion, 62.5 ng.kg-1.min-1) for 2 h (period 2). Whereas plasma glucose concentration dropped significantly during TNF infusion, endogenous glucose production did not change. The decrease in glucose concentrations was due to a stimulation of glucose clearance (P < 0.05). The rate of lipolysis did not decrease significantly, but free fatty acid (FFA) flux and plasma FFA concentration significantly decreased during TNF infusion (P < 0.05). The rate of appearance of leucine was not affected by TNF infusion, but TNF caused a significant increase in 13CO2 excretion (P < 0.05) and leucine oxidation (P < 0.05). The calculated rates of whole body protein synthesis decreased. We concluded that TNF did not directly affect glucose production. Furthermore, changes in protein and lipid kinetics during TNF infusion were not mediated by changes in insulin or glucagon and may have reflected direct effects of TNF.
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PMID:TNF directly stimulates glucose uptake and leucine oxidation and inhibits FFA flux in conscious dogs. 896 76

This study examined whether physiological changes in glucagon alter net hepatic glucose uptake (NHGU) or glycogen synthesis under conditions of hyperglycemia, hyperinsulinemia, and portal vein glucose concentrations exceeding those in the arterial circulation. Somatostatin was infused into 42-h-fasted dogs, insulin and glucagon were replaced intraportally at basal rates, and peripheral infusion of glucose maintained the hepatic glucose load twofold basal for 90 min (period 1). In period 2 (240 min) the insulin infusion was increased fourfold, glucose was infused intraportally, the hepatic glucose load was twofold basal, and glucagon was infused to create levels 150% basal (HiGGN, n = 6) or 40% basal (LoGGN, n = 6). NHGU rates (mg.kg-1.min-1) were low during period 1 (-0.9 +/- 0.7 in LoGGN and -0.2 +/- 0.4 in HiGGN, not significant) but increased during period 2 (-4.1 +/- 0.6 in LoGGN and -1.9 +/- 0.2 in HiGGN, P < 0.05). Endogenous glucose production (Endo Ra) declined during period 2 in LoGGN (P < 0.01 vs. basal) but did not change in HiGGN. Tracer-determined hepatic glucose uptake did not differ between groups. The poststudy increment in liver glycogen synthase I (12.5 +/- 3 vs. 6.5 +/- 2% of total) was greater in LoGGN (P < 0.05), as was net glycogen synthesis (27 +/- 8 vs. 13 +/- 3 mg/g liver, P = 0.06). An elevation in glucagon reduced NHGU (because of failure to suppress Endo Ra) and glycogen synthase activation and tended to reduce glycogen deposition.
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PMID:Physiological changes in circulating glucagon alter hepatic glucose disposition during portal glucose delivery. 931 37

The aim of this study was to determine whether the elimination of the hepatic arterial-portal (A-P) venous glucose gradient would alter the effects of portal glucose delivery on hepatic or peripheral glucose uptake. Three groups of 42-h-fasted conscious dogs (n = 7/group) were studied. After a 40-min basal period, somatostatin was infused peripherally along with intraportal insulin (7.2 pmol x kg(-1) x min(-1)) and glucagon (0.65 ng x kg(-1) x min(-1)). In test period 1 (90 min), glucose was infused into a peripheral vein to double the hepatic glucose load (HGL) in all groups. In test period 2 (90 min) of the control group (CONT), saline was infused intraportally; in the other two groups, glucose was infused intraportally (22.2 micromol x kg(-1) x min(-1)). In the second group (PD), saline was simultaneously infused into the hepatic artery; in the third group (PD+HAD), glucose was infused into the hepatic artery to eliminate the negative hepatic A-P glucose gradient. HGL was twofold basal in each test period. Net hepatic glucose uptake (NHGU) was 10.1 +/- 2.2 and 12.8 +/- 2.1 vs. 11.5 +/- 1.6 and 23.8 +/- 3.3* vs. 9.0 +/- 2.4 and 13.8 +/- 4.2 micromol x kg(-1) x min(-1) in the two periods of CONT, PD, and PD+HAD, respectively (* P < 0.05 vs. same test period in PD and PD+HAD). NHGU was 28.9 +/- 1.2 and 39.5 +/- 4.3 vs. 26.3 +/- 3.7 and 24.5 +/- 3.7* vs. 36.1 +/- 3.8 and 53.3 +/- 8.5 micromol x kg(-1) x min(-1) in the first and second periods of CONT, PD, and PD+HAD, respectively (* P < 0.05 vs. same test period in PD and PD+HAD). Thus the increment in NHGU and decrement in extrahepatic glucose uptake caused by the portal signal were significantly reduced by hepatic arterial glucose infusion. These results suggest that the hepatic arterial glucose level plays an important role in generation of the effect of portal glucose delivery on glucose uptake by liver and muscle.
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PMID:Importance of the hepatic arterial glucose level in generation of the portal signal in conscious dogs. 1091 27

The role of alpha- and beta-adrenergic receptor subtypes in mediating the actions of catecholamines on hepatic glucose production (HGP) was determined in sixteen 18-h-fasted conscious dogs maintained on a pancreatic clamp with basal insulin and glucagon. The experiment consisted of a 100-min equilibration, a 40-min basal, and two 90-min test periods in groups 1 and 2, plus a 60-min third test period in groups 3 and 4. In group 1 [alpha-blockade with norepinephrine (alpha-blo+NE)], phentolamine (2 microg x kg(-1) x min(-1)) was infused portally during both test periods, and NE (50 ng x kg(-1) x min(-1)) was infused portally at the start of test period 2. In group 2, beta-blockade with epinephrine (beta-blo+EPI), propranolol (1 microg x kg(-1) x min(-1)) was infused portally during both test periods, and EPI (8 ng x kg(-1) x min(-1)) was infused portally during test period 2. In group 3 (alpha(1)-blo+NE), prazosin (4 microg x kg(-1) x min(-1)) was infused portally during all test periods, and NE (50 and 100 ng x kg(-1) x min(-1)) was infused portally during test periods 2 and 3, respectively. In group 4 (beta(2)-blo+EPI), butoxamine (40 microg x kg(-1) x min(-1)) was infused portally during all test periods, and EPI (8 and 40 ng x kg(-1) x min(-1)) was infused portally during test periods 2 and 3, respectively. In the presence of alpha- or alpha(1)-adrenergic blockade, a selective rise in hepatic sinusoidal NE failed to increase net hepatic glucose output (NHGO). In a previous study, the same rate of portal NE infusion had increased NHGO by 1.6 +/- 0.3 mg x kg(-1) x min(-1). In the presence of beta- or beta(2)-adrenergic blockade, the selective rise in hepatic sinusoidal EPI caused by EPI infusion at 8 ng x kg(-1) x min(-1) also failed to increase NHGO. In a previous study, the same rate of EPI infusion had increased NHGO by 1.6 +/- 0.4 mg x kg(-1) x min(-1). In conclusion, in the conscious dog, the direct effects of NE and EPI on HGP are predominantly mediated through alpha(1)- and beta(2)-adrenergic receptors, respectively.
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PMID:The direct effects of catecholamines on hepatic glucose production occur via alpha(1)- and beta(2)-receptors in the dog. 1091 48

Infusion of glucose into the hepatic artery blocks the stimulatory effect of the "portal signal" on net hepatic glucose uptake (NHGU) during portal glucose delivery. We hypothesized that hepatic artery ligation (HAL) would result in enhanced NHGU during peripheral glucose infusion because the arterial glucose concentration would be perceived as lower than that in the portal vein. Fourteen dogs underwent HAL approximately 16 days before study. Conscious 42-h-fasted dogs received somatostatin, intraportal insulin, and glucagon infusions at fourfold basal and at basal rates, respectively, and peripheral glucose infusion to create hyperglycemia. After 90 min (period 1), seven dogs (HALpo) received intraportal glucose (3.8 mg. kg-1. min-1) and seven (HALpe) continued to receive only peripheral glucose for 90 min (period 2). These two groups were compared with nine non-HAL control dogs (control) treated as were HALpe. During period 2, the arterial plasma insulin concentrations (24 +/- 3, 20 +/- 1, and 24 +/- 2 microU/ml) and hepatic glucose loads (39.1 +/- 2.5, 43.8 +/- 2.9, and 37.7 +/- 3.7 mg. kg-1. min-1) were not different in HALpe, HALpo, and control, respectively. HALpo exhibited greater (P < 0.05) NHGU than HALpe and control (3.1 +/- 0.3, 2.0 +/- 0.4, and 2.0 +/- 0.1 mg. kg-1. min-1, respectively). Net hepatic carbon retention was approximately twofold greater (P < 0.05) in HALpo than in HALpe and control. NHGU and net hepatic glycogen synthesis during peripheral glucose infusion were not enhanced by HAL. Even though there exists an intrahepatic arterial reference site for the portal vein glucose concentration, the failure of HAL to result in enhanced NHGU during peripheral glucose infusion suggests the existence of one or more comparison sites outside the liver.
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PMID:Chronic hepatic artery ligation does not prevent liver from differentiating portal vs. peripheral glucose delivery. 1277 6

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