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)

Feeding problems, anorexia and vomiting are common in infants and children with chronic renal failure (CRF), and play a major role in the growth failure often found in this condition. However, the gastroenterological and nutritional aspects of CRF in children have received little attention, hence therapeutic interventions are usually empirical and often ineffective. Gastritis, duodenitis and peptic ulcer are often found in adults with CRF on regular haemodialysis and following renal transplantation. Despite persistent hypergastrinaemia, gastric acid secretion is decreased rather than increased in most of these patients, and active peptic disease appears to be promoted by the removal of the acid output inhibition (neutralisation of gastric acid by ammonia) that follows active treatment. Helicobacter pylori, on the other hand, does not seem to play a significant role in the pathogenesis of peptic disease in CRF. Gastro-oesophageal reflux has been found in about 70% of infants and children with CRF suffering from vomiting and feeding problems, and thus appears to be a major problem in these patients. In a number of symptomatic patients with CRF, gastric dysrhythmias and delayed gastric emptying have also been found; hence there appears to be a complex disorder of gastrointestinal motility in CRF. Serum levels of several polypeptide hormones involved in the modulation of gastrointestinal motility [e.g. gastrin, cholecystokinin (CCK), neurotensin] and the regulation of hunger and satiety (e.g. glucagon, CCK) are significantly raised as a consequence of renal insufficiency, and can be reverted to normal by renal transplantation. Furthermore, several other humoral abnormalities (e.g. hypercalcaemia, hypokalaemia, acidosis, etc.) are not uncommon in CRF. By directly affecting the smooth muscle of the gut or stimulating particular areas within the central nervous system, all these humoral alterations may well play a major role in the gastrointestinal dysmotility, anorexia, nausea and vomiting in patients with CRF. Specific pharmacological and nutritional interventions should thus be considered for the treatment of vomiting and feeding problems in CRF.
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PMID:Gastrointestinal function in chronic renal failure. 874 22

We have utilized both [5-15N]glutamine and [3-13C] pyruvate as metabolic tracers in order to: (i) examine the effect of pH, glucagon (GLU), or insulin on the precursor-product relationship between 15NH3, [15N]citrulline, and, thereby, [15N]urea synthesis and (ii) elucidate the mechanism(s) by which pyruvate stimulates [15N] urea synthesis. Hepatocytes isolated from rat were incubated at pH 6.8, 7.4, or 7.6 with 1 mM [5-15N]glutamine and 0.1 mM 14NH4Cl in the presence or the absence of [3-13C] pyruvate (2 mM). A separate series of experiments was performed at pH 7.4 in the presence of insulin or GLU. 15NH3 enrichment exceeded or was equal to that of [15N]citrulline under all conditions except for pH 7.6, when the 15N enrichment in citrulline exceeded that in ammonia. The formation of [15N]citrulline (atom % excess) was increased with higher pH. Flux through phosphate-dependent glutaminase (PDG) and [15N]urea synthesis were stimulated (p < 0.05) at pH 7.6 or with GLU and decreased (p < 0.05) at pH 6.8. Insulin had no significant effect on flux through PDG or on [15N]urea synthesis. Decreased [15N]urea production at pH 6.8 was associated with depleted aspartate and glutamate levels. Pyruvate attenuated this decrease in the aspartate and glutamate pools and stimulated [15N]urea synthesis. Production of Asp from pyruvate was increased with increasing medium pH. Approximately 80% of Asp was derived from [3-13C]pyruvate regardless of incubation pH or addition of hormone. Furthermore, approximately 20, 40, and 50% of the mitochondrial N-acetylglutamate (NAG) pool was derived from [3-13C]pyruvate at pH 6.8, 7.4, and 7.6, respectively. Both the concentration and formation of [13C]NAG from [3-13C]pyruvate were increased (p < 0.05) with glucagon and decreased (p < 0.05) with insulin or at pH 6.8. The data suggest a correlation between changes in [15N]urea synthesis and alterations in the level and synthesis of [13C]NAG from pyruvate. The current observations suggest that the stimulation of [15N]urea synthesis in acute alkalosis is mediated via increased flux through PDG and subsequent increased utilization of [5-15N] of glutamine for [15N]citrulline synthesis and/or increased synthesis of NAG from glutamate and pyruvate. The opposite may have occurred in acute acidosis. Glucagon, but not insulin, stimulated [15N]urea synthesis via increased flux through PDG and synthesis of NAG. Pyruvate stimulated urea synthesis via increased availability of aspartate and/or increased synthesis of NAG. The formation of NAG and aspartate from pyruvate are both pH-sensitive processes.
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PMID:Regulation of [15N]urea synthesis from [5-15N]glutamine. Role of pH, hormones, and pyruvate. 894 Jan 26

We studied the significance of donor nutritional status for hepatic rewarming injury and the usefulness of the glucagon loading test for the assessment of donor nutritional status in rats. In experiment 1, the animals were either free fed or fasted for 6, 24 or 48 h. The livers were preserved in chilled lactated Ringer's solution for 4 h and were divided into eight groups according to the fasting and rewarming periods. The ammonia level in the graft effluent was increased in grafts preserved for 24 h or longer, which was augmented when rewarming time was increased from 15 to 30 min (p < 0.05). In experiment 2, the animals were divided into four groups (n = 3 each) according to the fasting period. The hepatic tissue glycogen content was measured after fasting, and the serum glucose was measured after the administration of 50 micrograms/kg of glucagon i.v. The hepatic tissue glycogen content correlated with the increase rate of serum glucose (p = 0.0001). We conclude that glycogen may protect the hepatic graft from rewarming injury by improving energy status, particularly in prolonged rewarming. The glucagon loading test seems to be useful for assessing the glycogen content of the hepatic graft.
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PMID:Significance of donor nutritional status for rewarming injury of the hepatic graft in rats. 932 85

Chronic liver disease is often accompanied by hypoxaemia. We investigated the clinical factors that were related to the arterial oxygen tension (PaO2) in 40 women, all non-smokers with chronic liver disease. They were positive for hepatitis C virus (HCV) antibody and had no evidence of cardiopulmonary disease. Arterial blood was collected from patients at rest (> 15 min) for analysis of blood gases. We determined the correlation between blood gas tension and the clinical variables, i.e. the presence or absence of skin manifestations such as cutaneous spider nevi and palmar erythema, the presence or absence of splenomegaly, vital capacity, forced expiratory volume in one second, V25/body height, serum alanine aminotransferase (AST), serum asparate aminotransferase (ALT), serum cholinesterase, serum gamma-globulin/total protein, excretion of indocyanine green at 15 min (15-min retention rate, ICG level), blood level of ammonia, blood level of endotoxin, plasma level of glucagon and the serum level of type IV collagen-7S. The mean level of PaO2 was 78 +/- 11 (range: 43-95) torr. The mean alveolar-arterial oxygen tension gradient (A-aDO2) was 19 +/- 13 (range: 2-60) torr. Multiple regression analysis used PaO2 and A-aDO2 as objective variables, and the clinical findings as explanatory variables. The explanatory variables that were significantly correlated with blood gas values were ICG level, blood level of endotoxin and presence of skin manifestations. The ICG level showed a high correlation with blood gas values; the ICG level increased, the PaO2 decreased (r = -0.69), while the A-aDO2 showed a high positive correlation (r = +0.78, P < 0.001). Findings suggest that a reduction in hepatic blood flow and hepatocellular function interfere with the inactivation of vasoactive substances such as endotoxin by the liver, leading to the development of skin manifestations, the dilatation of intrapulmonary capillaries and the induction of hypoxaemia.
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PMID:Clinical factors that affect blood gases in non-smoking women with chronic liver disease. 951 26

We designed this study to determine whether the capacity of the liver to uptake ammonia and produce urea was affected by exercise (swimming at 24 degrees C with a 2.5% extra body-weight load). For this purpose, livers from sedentary rats at rest were perfused with a buffer containing increasing concentration of NH4Cl. The maximal hepatic capacity to produce urea was found at an NH4Cl concentration of 0.25 mM. Based on this finding all experiments with livers obtained from rats subject to swimming exercise were also carried out with a NH4Cl concentration of 0.25 mM. Thus, employing this concentration of ammonia, livers from sedentary and endurance trained rats, (for a period of 11 days ), that had either been resting or had been subjected to swimming exercise for 5 min or until exhaustion, were perfused in situ and ammonia uptake and urea production were measured. Clearly, both parameters were increased by exercise. However, these changes were not affected by swimming training. In addition, we demonstrate that the effect of an acute exercise on hepatic metabolism is not restricted to ammonia metabolism since livers from sedentary rats which had been subjected to swimming exercise for 5 min or until exhaustion showed higher urea production from L-glutamine. Our results also suggest that part of the changes in ureogenesis induced by exercise is mediated by cortisol (increased ammonia uptake) and part of the changes is mediated by glucagon (urea production).
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PMID:Swimming-exercise increases the capacity of perfused rat liver to produce urea from ammonia and L-glutamine. 1034 15

This study examines the role of glucagon and insulin in the incorporation of (15)N derived from (15)N-labeled glutamine into aspartate, citrulline and, thereby, [(15)N]urea isotopomers. Rat livers were perfused, in the nonrecirculating mode, with 0.3 mM NH(4)Cl and either 2-(15)N- or 5-(15)N-labeled glutamine (1 mM). The isotopic enrichment of the two nitrogenous precursor pools (ammonia and aspartate) involved in urea synthesis as well as the production of [(15)N]urea isotopomers were determined using gas chromatography-mass spectrometry. This information was used to examine the hypothesis that 5-N of glutamine is directly channeled to carbamyl phosphate (CP) synthesis. The results indicate that the predominant metabolic fate of [2-(15)N] and [5-(15)N]glutamine is incorporation into urea. Glucagon significantly stimulated the uptake of (15)N-labeled glutamine and its metabolism via phosphate-dependent glutaminase (PDG) to form U(m+1) and U(m+2) (urea containing one or two atoms of (15)N). However, insulin had little effect compared with control. The [5-(15)N]glutamine primarily entered into urea via ammonia incorporation into CP, whereas the [2-(15)N]glutamine was predominantly incorporated via aspartate. This is evident from the relative enrichments of aspartate and of citrulline generated from each substrate. Furthermore, the data indicate that the (15)NH(3) that was generated in the mitochondria by either PDG (from 5-(15)N) or glutamate dehydrogenase (from 2-(15)N) enjoys the same partition between incorporation into CP or exit from the mitochondria. Thus, there is no evidence for preferential access for ammonia that arises by the action of PDG to carbamyl-phosphate synthetase. To the contrary, we provide strong evidence that such ammonia is metabolized without any such metabolic channeling. The glucagon-induced increase in [(15)N]urea synthesis was associated with a significant elevation in hepatic N-acetylglutamate concentration. Therefore, the hormonal regulation of [(15)N]urea isotopomer production depends upon the coordinate action of the mitochondrial PDG pathway and the synthesis of N-acetylglutamate (an obligatory activator of CP). The current study may provide the theoretical and methodological foundations for in vivo investigations of the relationship between the hepatic urea cycle enzyme activities, the flux of (15)N-labeled glutamine into the urea cycle, and the production of urea isotopomers.
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PMID:Studies of hepatic glutamine metabolism in the perfused rat liver with (15)N-labeled glutamine. 1050 42

The effect of feed intake level (.6, 1.0, and 1.6 x maintenance energy and protein requirements, M) on splanchnic (portal-drained viscera [PDV] plus liver) metabolism was evaluated in six multicatheterized beef steers (398 +/- 27 kg), using a double 3 x 3 Latin square design. On the last day of each 21-d experimental period, six hourly blood samples were collected from arterial, portal, and hepatic vessels. Due to catheter patency, PDV fluxes were measured on five steers, and liver and splanchnic fluxes on four steers. Increasing intake elevated (P < .01) splanchnic release of total (T) amino acids (AA), through increases (P < .01) in PDV release of both essential (E) and nonessential (NE) AA, in spite of a tendency (P < .20) for increased liver removal of NEAA. The PDV release of AA N represented 27 and 51% of digested N for 1.0 and 1.6 x M, respectively. At 1.0 and 1.6 x M, the liver removed 34% of total AA released by the PDV. For individual AA, portal flux of most EAA increased (P < .05) with feed intake, and the increase (P < .10) in splanchnic flux was accompanied by increased arterial concentration for all EAA except histidine, lysine, and methionine. This suggests that these might be limiting AA for this diet. On a net basis, most individual NEAA were released by the PDV except glutamate and glutamine, which were removed by the digestive tract. There was a net removal of NEAA by the liver, except for aspartate and especially glutamate, which were released. Ammonia release by the PDV tended (P < .20) to increase with intake and represented 69, 53, and 45% of digested N at .6, 1.0, and 1.6 x M, respectively. Urea removed by the PDV, unaffected by intake, represented 32, 33, and 21% of the digested N. Arterial glucose concentration increased linearly (P < .01) with greater intake, whereas net liver and splanchnic glucose release increased in a quadratic (P < .05) manner. Net PDV glucose release represented 26% of net glucose hepatic release at 1.6 x M. Intake elevated (P < .10) both insulin and glucagon arterial concentrations, resulting from a larger increment of portal release (P < .01) than hepatic removal (P < .05). Intake-based variations in IGF-I and NEFA arterial concentrations (P < .05) were not related to changes in splanchnic metabolism. These results clearly show the crucial role of the splanchnic tissues in regulating the profile and quantity of AA and concentrations of glucose and pancreatic hormones reaching peripheral tissues.
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PMID:The effect of feed intake level on splanchnic metabolism in growing beef steers. 1078 2

In an experimental model of insulin-dependent diabetes mellitus (IDDM) in the teleost fish, the goby Gillichthys mirabilis, an isletectomy procedure completely removes the pancreatic endocrine tissue without affecting the exocrine acini or other essential tissues. Interestingly, isletectomized (Ix) gobies do not exhibit a significant hyperglycemia until 10-15 d after this procedure, suggesting a lack of initial diabetogenic actions of a pancreatic factor(s). Administering exogenous glucagon in otherwise nonsymptomatic 7-d Ix gobies, however, induces a hyperglycemic state comparable to that in severely diabetic rats or gobies (after 20 d post-Ix). The spontaneously arising hyperglycemia observed between 10 and 15d post-Ix, on the other hand, is significantly correlated with increasing serum cortisol concentrations, with both exhibiting sustained elevated levels (approx 23 mmol/L and >100 ng/mL, respectively) at 20- and 25-d post-Ix. Exogenous cortisol treatment also significantly induced hyperglycemia in nonsymptomatic, 7-d Ix gobies. By contrast, growth hormone (GH) had no detectable diabetogenic effect in 7-d Ix gobies. Serum levels of ammonia, the principal nitrogenous waste in this species, were not affected by glucagon treatment but were reduced slightly by GH treatment (30% reduction; p < 0.05). Cortisol treatment, on the other hand, increased ammonia levels twofold, suggesting that the glucocorticoid induces a negative nitrogen balance. These results indicate that the counterregulatory hormones--glucagon and cortisol--are effective diabetogenic factors in the Ix goby, capable of driving metabolic imbalance in this model of IDDM.
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PMID:Diabetogenic role of insulin's counterregulatory hormones in the isletectomized, diabetic goby. 1121 38

The effect of the supply of metabolizable protein on splanchnic fluxes of nutrients and hormones was measured in six catheterized late-lactation Holstein cows in a crossover design. Two isonitrogenous diets (16.3% CP), but differing in rumen protein degradability and estimated metabolizable protein (MP) supply (1654 g/ d, Lo-MP; 1930 g/d, Hi-MP) were fed, each over a 35-d experimental period. On d 34 or 35, net fluxes of nutrients and hormones across the portal-drained viscera, the liver, and total splanchnic tissues were determined. Portal absorption of total, essential, nonessential, and branched-chain amino acids (AA) increased with the Hi-MP diet. Approximately 76% of the additional metabolizable protein supply was recovered as extra AA-N absorption in the portal vein. Liver removal of AA was not different between diets, and this resulted in a greater net release across the splanchnic tissues for the Hi-MP diet. This extra AA supply provided substrates for the observed increased milk protein yield for the Hi-MP diet. Fractional efficiencies of conversion of absorbed individual essential AA into milk protein ranged from 0.42 to 0.68. The corresponding efficiencies for utilization of postsplanchnic AA supply were 0.42 to 1.80. Provision of methionine, phenylalanine, and histidine beyond the liver were similar to outputs in milk protein but the other essential AA were supplied to peripheral tissues in excess of milk output, indicative of oxidative mechanisms in nonhepatic tissues. Net fluxes of glucose, NH3-N, and urea were not affected by the diets. Neither arterial concentrations of insulin, somatotropin, or IGF-1, nor net transfers across the portal-drained viscera or liver of insulin, were affected by the diets. Although portal release of glucagon was not different between the diets, a smaller proportion was removed by the liver on the Hi-MP diet. Metabolism of AA across the splanchnic tissue bed is a major determinant of the quantity and the profile of AA delivered to peripheral tissues.
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PMID:Effect of supply of metabolizable protein on splanchnic fluxes of nutrients and hormones in lactating dairy cows. 1241 16

The objective of this work was to construct a dynamic model of hepatic amino acid metabolism in the lactating dairy cow that could be parameterized using net flow data from in vivo experiments. The model considers 22 amino acids, ammonia, urea, and 13 energetic metabolites, and was parameterized using a steady-state balance model and two in vivo, net flow experiments conducted with mid-lactation dairy cows. Extracellular flows were derived directly from the observed data. An optimization routine was used to derive nine intracellular flows. The resulting dynamic model was found to be stable across a range of inputs suggesting that it can be perturbed and applied to other physiological states. Although nitrogen was generally in balance, leucine was in slight deficit compared to predicted needs for export protein synthesis, suggesting that an alternative source of leucine (e.g. peptides) was utilized. Simulations of varying glucagon concentrations indicated that an additional 5 mol/d of glucose could be synthesized at the reference substrate concentrations and blood flows. The increased glucose production was supported by increased removal from blood of lactate, glutamate, aspartate, alanine, asparagine, and glutamine. As glucose output increased, ketone body and acetate release increased while CO(2) release declined. The pattern of amino acids appearing in hepatic vein blood was affected by changes in amino acid concentration in portal vein blood, portal blood flow rate and glucagon concentration, with methionine and phenylalanine being the most affected of essential amino acids. Experimental evidence is insufficient to determine whether essential amino acids are affected by varying gluconeogenic demands.
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PMID:An integrative model of amino acid metabolism in the liver of the lactating dairy cow. 1509 21


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