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)

This study characterized the cecal ligation and puncture (CLP) model of sepsis and the bolus endotoxin model of sepsis in rats with regard to specific hormonal, metabolic, and glucoregulatory changes which occur during the early, compensatory phases of sepsis. Plasma levels of glucose, lactate, insulin, and glucagon were measured during the initial 5 hr of endotoxicosis and CLP sepsis. During this time period, endotoxic and CLP septic rats displayed similar metabolic changes, particularly hyperglycemia, hyperlactacidemia, hyperinsulinemia, and hyperglucagonemia relative to their respective control groups. The metabolic and hormonal similarities observed between these two models of sepsis are consistent with the concept that endotoxin plays a role as a mediator of human and animal sepsis.
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PMID:Glucoregulatory, hormonal, and metabolic responses to endotoxicosis or cecal ligation and puncture sepsis in the rat: a direct comparison. 219 17

Altered glucose metabolism is one of the commonly observed sequelae of sepsis and septic shock. The present investigation was undertaken to determine the role of endotoxin (ET) upon hepatocyte glucoregulation, by measuring the activity of pyruvate kinase (PK), a key glycolytic enzyme. Hepatocytes were exposed to endotoxin concentrations known to occur in vivo during sepsis, i.e., from 1 X 10(-14) to 1 X 10(-8) g/ml. The alteration of the enzyme activities after addition of epinephrine, glucagon, insulin and calcium ionophore A23187 with and without ET preincubation were also examined. ET alone decreased the PK activity by 12% at all concentrations tested. The basal inhibition of the enzyme caused by epinephrine (-48%) was partially blocked by ET preincubation above 1 X 10(-10) g/ml. There were no ET-(glucagon, calcium ionophore, insulin) interaction. These in vitro results do not support pyruvate kinase as a site of hepatic enzyme regulation defect in endotoxaemia.
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PMID:Endotoxin, epinephrine, glucagon, insulin and calcium ionophore A23187 modulation of pyruvate kinase activity in cultured rat hepatocytes. 226 25

Increased plasma levels of the catabolic hormones glucagon, epinephrine, and cortisol have been implicated in mediating various metabolic alterations in trauma and sepsis. Their role in altered protein turnover and amino acid transport in skeletal muscle during sepsis, however, is not known. In the current study, rats were infused with a mixture of the catabolic hormones for 16 hours. Control animals were infused with vehicle solution. Protein synthesis and degradation rates were measured in incubated, intact soleus muscles as incorporation of 14C-phenylalanine into protein and release of tyrosine into incubation medium, respectively. Muscle amino acid uptake was determined by measuring the intracellular to extracellular ratio of [3H]-alpha-aminoisobutyric acid after incubation for 2 hours. Infusion of catabolic hormones for 16 hours resulted in elevated plasma glucose and lactate levels, reduced plasma concentrations of most amino acids, and accelerated muscle protein breakdown, similar to previous findings in septic rats. Protein synthesis rates and amino acid uptake in incubated muscles were not significantly different in control and hormone-infused rats. The current study suggests that increased muscle proteolysis in sepsis and severe injury may be mediated in part by catabolic hormones. In contrast, reduced muscle protein synthesis and amino acid uptake are probably signaled by other substances or mechanisms.
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PMID:Effect of catabolic hormone infusion on protein turnover and amino acid uptake in skeletal muscle. 230 36

The intestinal metabolism of glucose and glutamine was studied in rats made septic by cecal ligation and puncture technique. Sepsis resulted in negative nitrogen balance and produced increases in the concentrations of blood pyruvate, lactate, alanine, and glutamine, and decreases in those of 3-hydroxybutyrate and acetoacetate. Both plasma insulin and glucagon concentrations were increased by 2.2- and 3.2-fold in septic rats, respectively. Portal-drained visceral blood flow increased in septic rats, and was accompanied by a decrease in the rates of utilization of glutamine and production of lactate, glutamate, and ammonia compared with those rates in sham-operated animals. Enterocytes isolated from septic rats showed decreased rates of glucose and glutamine utilization compared with cells isolated from corresponding controls. The maximal activities of hexokinase, 6-phosphofructokinase, pyruvate kinase, and glutaminase were decreased in intestinal mucosal scrapings of septic rats. It is concluded that a moderate form of sepsis decreases the rates of glucose and glutamine utilization (both in vivo and in vitro) by the epithelial cells of the small intestine. This may be caused by changes in the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells as a metabolic adaptation to spare glucose and glutamine for use by other tissues.
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PMID:Glucose and glutamine metabolism in the small intestine of septic rats. 236 28

The mediator(s) and mechanism(s) of acute-phase protein synthesis in the liver following injury and sepsis are not fully known. Elevated plasma levels of the catabolic hormones cortisol, glucagon, and epinephrine have been reported in trauma and sepsis. In previous reports, when these hormones were infused simultaneously (triple hormone infusion), several, but not all, of the metabolic alterations characteristic of sepsis occurred. In the current investigation, the effect of triple hormone infusion on hepatic protein synthesis was studied. Rats were infused intravenously during 16 hours with a solution containing corticosterone (4.2 mg/kg/h), glucagon (2.5 micrograms/kg/h), and epinephrine (6 micrograms/kg/h). Control animals were infused with a corresponding volume of vehicle. Total hepatic protein synthesis in vivo was measured with a flooding dose technique using [14C]-leucine. The synthesis of total secretory proteins and of the individual proteins albumin, complement component C3, and alpha 1-acid glycoprotein was measured in isolated, perfused liver using [3H]-leucine and a recirculating technique. Urinary excretion of nitrogen and plasma concentration of glucose were higher and plasma total amino acid concentration was lower in hormone-infused than in control rats. Total hepatic protein synthesis in vivo, expressed as the proportion of the protein pool that was replaced each day, was increased from 39% +/- 2% per day to 48% +/- 3% per day (P less than .05) by hormone infusion, but synthesis of secretory proteins in perfused liver was not significantly altered. The results suggest that although total hepatic protein synthesis may be increased by catabolic hormones, other mediator(s) are probably responsible for the stimulation of acute-phase protein synthesis in sepsis.
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PMID:Protein synthesis in liver following infusion of the catabolic hormones corticosterone, epinephrine, and glucagon in rats. 247 64

The acute metabolic response following experimentally induced sepsis can generally be classified as either hypodynamic ("low flow") or hyperdynamic ("high flow"). We have found that in conscious guinea pigs the bolus infusion of 10(10) live Escherichia coli bacteria can elicit either response, depending on the route of administration of the bacteria. Intravenous infusion results in the hypodynamic condition of septic shock in which oxygen consumption (VO2) is reduced to approximately 60% of the control level, plasma glucose is elevated 4 hr after infusion with a reversal to extreme hypoglycemia 12 hr after infusion, and body temperature is reduced by approximately 5 degrees C in 12 hr. In contrast, subcutaneous injection results in increased VO2, body temperature, and plasma glucose. In both models the concentration of cortisol, catecholamines and glucagon were elevated, but the responses were more pronounced in the hypodynamic model. In both cases, insulin concentration was decreased. These models of sepsis are useful because many aspects of response are comparable to man, they are simple to create, and they are consistent and reproducible.
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PMID:Hyper and hypodynamic models of sepsis in guinea pigs. 249 5

Intestinal mucosal atrophy, as induced by total parenteral nutrition (TPN) and/or prolonged bowel rest, is hypothesized to enhance bowel endotoxin (LPS) translocation and may alter host responses to infection. To examine the effect of TPN-induced bowel atrophy on the response to LPS, 12 healthy volunteers were randomized to receive either enteral feedings (ENT, n = 6) or seven days of TPN without oral intake (TPN, n = 6). Enteral or TPN feedings were terminated 12 hours before the study period when a constant dextrose infusion (50 mg/kg/hour) was initiated and continued throughout the subsequent study period. After placement of arterial, hepatic vein, and femoral vein catheters, metabolic parameters were determined before and for six hours after an intravenous E. coli LPS challenge (20 U/kg). Subsequent peak levels of arterial glucagon (ENT, 189 +/- 39 pg/mL; TPN, 428 +/- 48; p less than 0.01), arterial epinephrine (ENT, 236 +/- 52 pg/mL; TPN, 379 +/- 49; p less than 0.05) and hepatic venous cachectin/tumor necrosis factor (cachectin/TNF) (ENT, 250 +/- 56 pg/mL; TPN, 479 +/- 136; p less than 0.05) were significantly higher in the TPN group than in the ENT group. The extremity efflux of lactate (ENT, -16 +/- 4 micrograms/min-100cc tissue; TPN, -52 +/- 13; t = 2 hours; p less than 0.05) and of amino acids (ENT, -334 +/- 77 nmol/min-100cc tissue; TPN, -884 +/- 58; t = 4 hours; p less than 0.05) were higher in the TPN subjects after the endotoxin challenge. Circulating C-reactive Protein (CRP) levels measured 24 hours postendotoxin were also significantly higher in the TPN subjects (ENT, 1.7 +/- 0.2 mg/dL; TPN, 3.2 +/- 0.3; p less than 0.01). Hence the counter-regulatory hormone and splanchnic cytokine responses to LPS were enhanced after TPN and bowel rest. This is associated with a magnified acute-phase response, peripheral amino acid mobilization, and peripheral lactate production. Thus antecedent TPN may influence the metabolic alterations seen in infection and sepsis via both an exaggerated counter-regulatory hormone response as well as an enhanced systemic and splanchnic production of cytokines.
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PMID:Total parenteral nutrition and bowel rest modify the metabolic response to endotoxin in humans. 250 83

Multiple-system organ failure is associated with progressive defects of cellular metabolism involving several organ systems. The metabolic failure is caused by a neural-hormonal reaction to trauma and sepsis and by humoral mediators damaging cell metabolism. Involved are catabolic hormones like catecholamines, cortisol and glucagon as well as the humoral mediators interleukin and arachidonic acid metabolites. There is an increase in resting energy expenditure and a derangement of utilization and production of adenine nucleotides. Severe injury, sepsis and multiple-system organ failure are associated with a 30-40% decreased content of energy rich phosphates in different tissues. The low energy charge potential is caused by the inability to use nutritional substrates adequately. Relative clearance and oxidation of glucose will advance fatty infiltration of the liver. Clearance and oxidation of fat is normal or often increased. If illness is progredient fat utilization will be disturbed. Although protein synthesis is increased in critical ill patients, due to excessive proteolyses net protein loss occur. In preterminal patients the ability of the liver to synthetize protein decreases, concentrations of several free amino acids in plasma increase, while the clearance for amino acids decreases.
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PMID:[Metabolic problems and therapeutic approaches in multiple organ failure]. 251 May 39

The plasma concentration of various catabolic hormones, including glucagon and catecholamines, is elevated in sepsis. Furthermore, the infusion of these hormones into control animals increases the rate of glucose production. Previous studies by our laboratory have demonstrated that adrenergic blockade alone is not able to reverse or prevent the sepsis-induced increase in glucose metabolism. Therefore, the purpose of the present study was to determine whether the sepsis-induced hyperglucagonemia was important to maintain the elevation in glucose metabolism. Hypermetabolic sepsis was produced in chronically catheterized conscious rats by repeated subcutaneous injections of Escherichia coli. Glucose kinetics, assessed by the constant i.v. infusion of [6-3H]- and [U-14C]-glucose, were determined in septic and nonseptic rats prior to and for 3-4 hr after the infusion of somatostatin with or without insulin replacement. Sepsis increased the rate of glucose appearance (80%), recycling (276%), and metabolic clearance (88%), as well as the plasma lactate concentration (140%), compared to nonseptic rats. Lowering both the insulin and glucagon concentration with somatostatin did not attenuate the sepsis-induced increases in glucose metabolism. However, when the hyperglucagonemia was selectively reduced by replacing insulin, and euglycemia was maintained by a glucose infusion, the elevated rate of endogenous glucose production returned to levels not different from nonseptic animals. In contrast, the sepsis-induced elevation of glucose clearance was unaltered under these conditions. These results indicate that during hypermetabolic sepsis the elevated glucagon level is an important mediator of the enhanced rate of gluconeogenesis.
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PMID:Importance of hyperglucagonemia in eliciting the sepsis-induced increase in glucose production. 257 79

The purpose of this study was to investigate possible alterations induced by sepsis and endotoxicosis in the late phase of Ca2+-dependent signaling in rat liver. Hepatocytes isolated from septic or chronically endotoxin (ET)-treated rats were labeled with [32P]H3PO4 and stimulated with various agents. Proteins were resolved by one-dimensional polyacrylamide gel electrophoresis and autoradiographed. Vasopressin (VP)- and phenylephrine (PE)-induced responses were attenuated in both septic and ET-treated rats for cytosolic and membrane proteins compared with their respective controls. Glucagon and 12-O-myristate phorbol-13-acetate (TPA) affected only the phosphorylation of membrane proteins. Glucagon-induced changes in the phosphorylation of membrane proteins were affected by both sepsis and endotoxicosis, whereas TPA-stimulated phosphorylation was lowered only in endotoxicosis. Response to the Ca2+ ionophore A23187 was depressed in septic rats for cytosolic proteins. The phosphorylation of two cytosolic proteins, i.e., 93 and 61 kDa (previously identified as glycogen phosphorylase and pyruvate kinase, respectively), in response to VP, PE, and A23187 was severely impaired by endotoxicosis and sepsis. TPA did not affect the phosphorylation state of these two proteins. The results show that sepsis and endotoxicosis produce perturbations of the phosphorylation step in Ca2+ transmembrane signaling. Such changes can explain alterations of glycogenolysis and gluconeogenesis associated with sepsis and endotoxicosis.
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PMID:Protein phosphorylation in isolated hepatocytes of septic and endotoxemic rats. 258 48


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