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)

1. The metabolism of glutamine and alanine in the lung was studied in rats made septic by a caecal ligation and puncture technique. 2. The blood glucose concentration was not significantly different in septic rats, but blood pyruvate, lactate, glutamine and alanine concentrations were markedly increased as compared with sham-operated rats. Conversely, blood ketone body and plasma cholesterol concentrations were significantly decreased in septic rats. Both plasma insulin and plasma glucagon concentrations were markedly elevated in response to sepsis. Sepsis resulted in a negative nitrogen balance. 3. Sepsis increased the rates of production of glutamine (52.5%, P less than 0.001), alanine (38.9%, P less than 0.001) and glutamate (48.6%, P less than 0.001) by lung slices incubated in vitro. 4. Sepsis increased lung blood flow by 27.6% (P less than 0.05). Blood flow and arteriovenous concentration difference measurement across the lung of septic rats showed an increase in the net exchange rates of glutamine (142.5%, P less than 0.001), alanine (129.4%, P less than 0.001), glutamate (100.9%, P less than 0.001) and ammonia (138.0%, P less than 0.001) as compared with sham-operated control rats. 5. Sepsis produced significant decreases in the lung concentrations of glutamine (36.8%), glutamate (20.8%), 2-oxoglutarate (64.8%) and AMP (18.3%). The lung concentrations of alanine (95.9%), ammonia (67.7%) and pyruvate (89.7%) were increased. 6. The maximal activities of glutamine synthetase (20.4%, P less than 0.05), phosphate-dependent glutaminase (18.9%, P less than 0.05) and alanine aminotransferase (25.5%, P less than 0.05) were increased, but there was no marked change in that of glutamate dehydrogenase, in the lungs of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine and alanine metabolism in lungs of septic rats. 168 36

Ornithine alpha-ketoglutarate (OKG) has been useful as an adjuvant of enteral and parenteral nutrition. However, its metabolism and mechanism of action remain unclear although it is known that alpha-ketoglutarate (alpha KG) and ornithine (ORN) follow, in part, common metabolic pathways. Six fasting healthy male subjects underwent three separate oral load tests: (i) they received 10 g of OKG (i.e., 3.6 g of alpha KG and 6.4 g of ORN); (ii) 6.4 g of ORN as ornithine hydrochloride, and (iii) 3.6 g of alpha KG as calcium alpha-ketoglutarate. Blood was drawn 15 times over a five-hour period for measurements of plasma amino acids, alpha KG, insulin, and glucagon. After OKG and ORN administration, plasma ORN peaked at 60-75 min (494 +/- 91 and 541 +/- 85 mumol/L). The increase in plasma alpha KG was very small. OKG, alpha KG, and ORN all increased glutamate concentrations at 60 min (mean: +43%, +68%, +68%, respectively, p less than 0.05 compared to basal values). However, only OKG increased proline and arginine levels at 60 min (mean: +35%, p less than 0.01 and mean: +41%, p less than 0.05). Furthermore, glutamate, proline, and arginine concentrations correlated linearly with ornithine levels at 60 min. Finally, OKG increased insulinemia and glucagonemia (mean: +24% at 15 min, p less than 0.05 and +30% at 60 min, p less than 0.01, respectively). These data provide evidence that the combination of ORN and alpha KG modifies amino acid metabolism in a way which is not observed when they are administered separately. In addition, the OKG-mediated increase in insulin levels probably does not appear to result from a direct action of ORN on pancreatic secretion.
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PMID:Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects. 240 64

The hypothesis that the anxiety induced by repeated injections affects brain energy metabolism was tested. Normal 19- to 21-day-old mice were stressed by two sham intraperitoneal injections within 4 min, at which time they were decapitated. Noninjected, control littermates were quickly decapitated. Momentary stress increased plasma glucose (12%), glycerol (85%), beta-hydroxybutyrate (108%), and lactate (153%)--a reflection of elevated plasma cortisol (25%) and glucagon (45%). In brain, stress increased levels of glucose-6-P (15%) and fructose-6-P (17%). The brain pyruvate concentration increased 74%; lactate 76%. Citrate, alpha-ketoglutarate, and malate increased 15, 95, and 37%, respectively. Levels of glycogen, glucose, phosphocreatine, ATP, ADP, and AMP were unchanged. The brain lactate/pyruvate ratio was normal but the brain/plasma lactate ratio fell 32%. Metabolite changes in the stressed animals were compatible with a decrease in the glycolytic flux at the phosphofructokinase step and a paradoxical increased flux in the Krebs citric acid cycle. The decreased brain/plasma lactate ratio supported increased uptake of lactate from plasma and increased brain lactate oxidation. Metabolite changes similar to those described above occurred in unstressed mice injected with lactate. Findings confirm a positive effect of stress on brain metabolism, support a role for lactate as an oxidative fuel for brain, and caution that the rate of cerebral glucose utilization may not always reflect brain energy (oxidative) metabolism accurately.
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PMID:Effect of momentary stress on brain energy metabolism in weanling mice: apparent use of lactate as cerebral metabolic fuel concomitant with a decrease in brain glucose utilization. 279 72

The metabolic flux through the alpha-ketoglutarate dehydrogenase reaction in perfused livers was monitored by measuring the rate of 14CO2 production from [1-14C]alpha-ketoglutarate. The rates of 14CO2 production and glucose production from [1-14C]alpha-ketoglutarate were increased with increasing perfusate alpha-ketoglutarate concentrations. Vasopressin, angiotensin II, and the alpha 1-adrenergic agonist phenylephrine stimulated transiently by 2.5-fold the metabolic flux through the alpha-ketoglutarate dehydrogenase reaction in the presence and absence of Ca2+ in the perfusion medium. High concentrations of glucagon (1 x 10(-8) M) and 8-p-chlorophenylthio-cAMP (100 microM) (data not shown) also stimulated transiently the metabolic flux through the alpha-ketoglutarate dehydrogenase reaction. However, lower glucagon concentrations (1 x 10(-9) M) stimulated the rate of 14CO2 production from [1-14C]alpha-ketoglutarate only under conditions optimized to fix the cellular oxidation-reduction state at an intermediate level, when glucagon (1 x 10(-9) M)-mediated elevation of cAMP content was greater than that observed under highly oxidizing and reducing conditions. These data indicate that agonists which increase cytosolic free Ca2+ levels stimulate the metabolic flux through the alpha-ketoglutarate dehydrogenase complex. Furthermore, the data presented here demonstrate for the first time that physiological glucagon concentrations stimulate the metabolic flux through the alpha-ketoglutarate dehydrogenase reaction only under conditions known to be optimal for glucagon-mediated Ca2+ mobilization in the isolated perfused rat liver.
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PMID:Hormonal regulation of the alpha-ketoglutarate dehydrogenase complex in the isolated perfused rat liver. 283 12

Isolated mouse liver mitochondria incubated with streptozotocin showed decreased rate and extent of Ca2+ uptake, and, dependent on the concentration of streptozotocin and the addition of alpha-ketoglutarate, glutamate, fluorocitrate or guanosine 5'-triphosphate, the retention of Ca2+ was either increased or decreased. Similar observations were made in liver mitochondria incubated with succinyl-CoA. In mitochondria isolated from the kidneys and islets of mice injected with streptozotocin, with and without additional injections of glucose and/or glucagon, the rate and extent of Ca2+ uptake were reduced and the release of accumulated Ca2+ was stimulated. Electron microscopy and X-ray microanalysis showed dislocation of Ca2+-containing precipitates from the mitochondria to the cytosol, and stereology disclosed increased mitochondrial volume in the B cells of streptozotocin-treated mice. State 3 and state 4 respiration with NAD-linked substrates was inhibited, but succinate oxidation was unaffected, in mitochondria isolated from the kidneys of mice treated with streptozotocin. In the kidneys of streptozotocin-injected mice, the concentration of succinyl-CoA was increased, that of citrate and guanosine 5'-triphosphate was decreased, that of glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-diphosphate was unaffected, and the metabolite concentration ratios suggested increased mitochondrial [NAD+]/[NADH] ratio and decreased cytoplasmic [NAD+]/[NADH] ratio. It is suggested as a new hypothesis that the cytotoxicity and the diabetogenicity of streptozotocin are dependent on inhibited citric acid cycle enzyme activity (primarily that of succinyl-CoA synthetase and citrate synthetase) with altered metabolite concentrations, leading to impairment of the mitochondrial uptake of Ca2+ and the activation of the pyruvate, isocitrate and alpha-ketoglutarate dehydrogenases.
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PMID:Mitochondrial changes and associated alterations induced in mice by streptozotocin administered in vivo and in vitro. 288 8

The role of Ca2+ in stimulation of the malate-aspartate shuttle by norepinephrine and vasopressin was studied in perfused rat liver. Shuttle capacity was indexed by measuring the changes in both the rate of production of glucose from sorbitol and the ratio of lactate to pyruvate during the oxidation of ethanol. (T. Sugano et al. (1986) Amer. J. Physiol. 251, E385-E392). Asparagine (0.5 mM), but not alanine (0.5 mM) decreased the ethanol-induced responses. Norepinephrine and vasopressin had no effect on the ethanol-induced responses when the liver was perfused with sorbitol or glycerol. In the presence of 0.25 mM alanine, norepinephrine, vasopressin, and A23187 decreased the ethanol-induced responses that occurred with the increase of flux of Ca2+. In liver perfused with Ca2+-free medium, asparagine also decreased the ethanol-induced responses, but norepinephrine and vasopressin had no effect. Aminooxyacetate inhibited the effects of norepinephrine, A23187, and asparagine. Regardless of the presence or absence of perfusate Ca2+, the combination of glucagon and alanine had no effect on the ethanol-induced responses. Norepinephrine caused a decrease in levels of alpha-ketoglutarate, aspartate, and glutamate in hepatocytes incubated with Ca2+. The present data suggest that the redistribution of cellular Ca2+ may activate the efflux of aspartate from mitochondria in rat liver, resulting in an increase in the capacity of the malate-aspartate shuttle.
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PMID:Ca2+-dependent activation of the malate-aspartate shuttle by norepinephrine and vasopressin in perfused rat liver. 289 18

Data from a number of laboratories suggest that the exchange of glutamate for aspartate across the mitochondrial inner membrane is stimulated by glucagon and by Ca2+-mobilizing hormones. The purpose of this study was to determine the site of action of these hormones. Two possibilities were considered and tested. The first hypothesis is that the mitochondrial membrane electrical potential gradient (delta psi m) in the cells is increased by the hormones; and that the putative increase in delta psi m stimulates aspartate efflux. The second possibility is that Ca2+ mediates decreases in cellular levels of alpha-ketoglutarate, secondary to stimulation of alpha-ketoglutarate dehydrogenase, and that the decrease in alpha-ketoglutarate stimulates aspartate production by mitochondria. The effect of glucagon on delta psi m was estimated in intact hepatocytes using the lipophilic cation tetraphenyl phosphonium. No increase in delta psi m was observed due to hormone treatment. On the other hand, alpha-ketoglutarate was found to be an effective competitive inhibitor of aspartate formation via glutamate transamination by isolated liver mitochondria (Ki = 0.55 mM).
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PMID:Sites of action of glucagon and other Ca2+ mobilizing hormones on the malate aspartate cycle. 289 19

The transport of Ca2+ in islet and kidney mitochondria respiring on succinate was inhibited by atractylate and fluorocitrate, and stimulated by pyruvate, isocitrate, alpha-ketoglutarate, dibutyryl cAMP, oligomycin and bongkrekate, and by in vivo administration of glucagon, glyceraldehyde or glucose. The kidney [beta-hydroxybutyrate]/[acetoacetate] ratio was increased in glyceraldehyde treated mice. The data suggest a relationship, which might be influenced by cAMP, between activity of pyruvate, isocitrate and alpha-ketoglutarate dehydrogenases and transport of Ca2+ in islet and kidney mitochondria. A contributory role of reductive carboxylation for Ca2+ uptake, and a role of citrate for Ca2+ retention are discussed.
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PMID:Factors affecting Ca2+ transport in mouse islet and kidney mitochondria. 301 50

The effects of glucagon infusion on substrate oxidation by liver mitochondria from the pigeon, Columba livia, were examined. While the response of mammalian liver mitochondria to glucagon involves elevated rates of oxidation of succinate, pyruvate, alpha-ketoglutarate, glutamate, and acyl carnitines, avian hepatic mitochondria demonstrate no change in state 3 rates for the oxidation of succinate, pyruvate, alpha-ketoglutarate, and glutamate upon glucagon infusion. There was a trend toward decreasing the state 3 rate of oxidation of long-chain acyl carnitines compared to other substrates with glucagon treatment. State 4 rates of oxidation of all substrates including acyl carnitines were unaffected by glucagon infusion. The permeability of pigeon liver mitochondria to NADH was not affected by glucagon infusion, indicating no change in the fragility of the mitochondria. The effect of glucagon in elevating oxidation of lipids in mammals and decreasing oxidation in birds correlates with its hyperlipemic action in birds and the hypolipemic action in mammals.
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PMID:The effects of glucagon on hepatic mitochondrial metabolism in the pigeon, Columba livia. 318 36

Plasma concentrations of glucose, insulin, C-peptide, glucagon, cortisol and hGH were measured in burn patients (mean burn surface area 21 per cent) treated or not with ornithine alpha-ketoglutarate (OKG). An increase in basal values of glucose, insulin, C-peptide and cortisol was demonstrated in both groups, whereas hGH values diminished. OKG modified neither insulin nor hGH values 24 h after its enteral administration nor insulin levels within the first 4 h after intake. On the other hand, 60 min after enteral nutrition was restarted the hyperglycaemia observed in untreated subjects was reduced by OKG whereas a hyperinsulinism was observed in both groups. These results suggest that: (i) the anticatabolic/anabolic action of OKG in burn patients is not mediated by insulin or hGH, (ii) OKG probably induces an increase in glucose tolerance in burn patients, in whom there is a state of insulin resistance. The mechanism of this action requires further study.
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PMID:Influence of enterally administered ornithine alpha-ketoglutarate on hormonal patterns in burn patients. 332 11


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