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)

Plasma glucagon rises after major injury and could act to increase gluconeogenesis and ureagenesis in the post-traumatic state. This study documents the effect of prolonged glucagon infusion on ureagenesis and nitrogen excretion, as well as possible sources of the increased ureagenesis, in normal man. Four healthy men fasted for 6 days during intravenous infusion of glucose (750 gmday), establishing a steady state of minimal ureagenesis. Glucagon (1 mg/day) then was added to the infusion for 5 days. Glucose alone was given for the final 2 days. Forearm muscle flux of metabolites was determined by standard arterial-deep venous sampling and capacitance plethysmography. Glucagon concentration was suppressed during glucose infusion (11 +/- 13 pg/ml) and rose to levels seen in subjects with major trauma during glucagon infusion (669 +/- 138 pg/ml). Glucose infusion stabilized urine nitrogen excretion at 1.54 +/- 0.42 gm of N/sq m/day. Nitrogen excretion increased to 2.40 +/- 0.53 gm of N/sq m/day with glucagon infusion, with urea accounting for the increased excretion. Excretion of 3-methylhistidine was unchanged. Plasma amino acid concentration was strikingly reduced on the first day of glucagon infusion, where it stabilized. Forearm flux showed a slight net release of amino acid nitrogen during glucose infusion. Addition of glucagon to the glucose infusion resulted in a net uptake of nitrogen by forearm skeletal muscle. These evidences strong suggest that glucagon infusion in normal man increases ureagenesis, not only at the expense of the free amino acid pool, but by the hydrolysis of visceral protein as well, with muscle protein being maintained.
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PMID:The effects of glucagon on protein metabolism in normal man. 38 36

In order to assess the role of glucagon in human protein metabolism and to examine its action as a "catabolic" hormone, studies were conducted in two normal male subjects over an 8-day period. After minimum and stable urinary nitrogen excretion had been produced by the continuous nasogastric administration of carbohydrate (720 g/day) for 8 consecutive days, a continuous intravenous infusion of glucagon (1.0 mg/24 hr) was superimposed on days 7 and 8. Excretion of total nitrogen (N) and urea-N increased significantly (p less than 0.05). Excretion of 3-methylhistidine was unaltered, suggesting that the source of the N losses produced by glucagon did not derive from increased muscle proteolysis. Although striking hypoaminoacidemia was produced, the reductions of extracellular amino acids alone could not account for all of the extra urea excreted. These data suggest that hyperglucagonemia in normal man induces mild nitrogen losses by stimulation of hepatic ureogenesis from free intracellular amino acid pools and not by increased rates of muscle protein breakdown.
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PMID:Glucagon infusion in normal man: effects on 3-methylhistidine excretion and plasma amino acids. 40 91

In a randomised controlled trial, preterm babies undergoing ligation of a patent ductus arteriosus were given nitrous oxide and d-tubocurarine, with (n = 8) or without (n = 8) the addition of fentanyl (10 micrograms/kg intravenously) to the anaesthetic regimen. Major hormonal responses to surgery, as indicated by changes in plasma adrenaline, noradrenaline, glucagon, aldosterone, corticosterone, 11-deoxycorticosterone, and 11-deoxycortisol levels, in the insulin/glucagon, molar ratio, and in blood glucose, lactate, and pyruvate concentrations were significantly greater in the non-fentanyl than in the fentanyl group. The urinary 3-methylhistidine/creatinine ratios were significantly greater in the non-fentanyl group on the second and third postoperative days. Compared with the fentanyl group, the non-fentanyl group had circulatory and metabolic complications postoperatively. The findings indicate that preterm babies mount a substantial stress response to surgery under anaesthesia with nitrous oxide and curare and that prevention of this response by fentanyl anaesthesia may be associated with an improved postoperative outcome.
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PMID:Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. 2092 62

The effect of major operative trauma on skeletal muscle metabolism was examined in nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acids/m2/day) for 5 days before and 4 days after an operation. Compared with the preoperative state, 72 hours after the operation there was a significant rise in arterial levels of glucagon, cortisol, norepinephrine, and inactive triiodothyronine and a drop in concentrations of insulin, active triiodothyronine, and amino acids. Forearm blood flow increased, as well as the efflux from forearm muscle of lactate, taurine, serine, glycine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, arginine, and total amino acid nitrogen (440%). This loss of muscle protein after trauma is associated with increased muscle proteolysis, as measured by increased urinary 3-methylhistidine excretion (83%), and accounts for increased nitrogen loss (54%) from the body. Increased activity of the sympathetic nervous system is manifested by increased levels of epinephrine and norepinephrine, a relative lack of insulin, and increased levels of glucagon. This hormonal milieu plays an important role in the production of hypoaminoacidemia, increased efflux of amino acids and lactate from muscle, and negative nitrogen balance observed in these traumatized patients.
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PMID:Major operative trauma increases peripheral amino acid release during the steady-state infusion of total parenteral nutrition in man. 308 29

Concern about the side effects of various anaesthetic agents in newborn infants has led to the widespread use of anaesthesia with unsupplemented nitrous oxide and oxygen with muscle relaxants in such patients. To investigate the efficacy of such a regimen 36 neonates undergoing operations were randomised to two groups: one group received anaesthesia with nitrous oxide and curare alone and the other was additionally given halothane. Concentrations of metabolites and hormones were measured before and at the end of operation and at six, 12, and 24 hours after operation and the values compared between the two groups. Neonates given halothane anaesthesia showed decreased hormonal responses to operation, with significant differences between the two groups in the changes in adrenaline, noradrenaline, and cortisol concentrations and the ratio of insulin to glucagon concentration. Changes in blood concentrations of glucose and total ketone bodies and plasma concentrations of non-esterified fatty acids were also decreased in neonates receiving halothane anaesthesia. Neonates given anaesthesia with unsupplemented nitrous oxide showed significantly greater increases in the urinary ratio of 3-methylhistidine to creatinine concentration and their clinical condition was also more unstable during and after operation. Unless specifically contraindicated potent anaesthesia with halothane or other anaesthetic agents should be given to all neonates undergoing surgical operations as it decreases their stress responses and improves their clinical stability during and after operation.
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PMID:Does halothane anaesthesia decrease the metabolic and endocrine stress responses of newborn infants undergoing operation? 312 62

In an attempt to define the relationship between tumor burden (cachexia) and host hepatocyte gluconeogenesis, the following experiments were performed with the use of an F344 male rat bearing a transplantable sarcoma. Food intake of tumor-bearing (TB) rats was constant until day 24 following implant and a tumor burden of 18 +/- 5.2% (mean +/- SD), at which time food intake progressively declined daily. Tumor burden was arbitrarily divided at 12.8% to determine if any measured changes occurred prior to or following the approximate time when a significant decline in food intake occurred. Plasma glucose levels decreased with tumor burden. Whole-blood lactate levels increased with tumor burden. Fasting plasma alanine levels decreased with tumor burden. Plasma 3-methylhistidine levels increased with tumor burden. Plasma glucagon levels increased with tumor burden, whereas plasma insulin levels decreased. Hormone changes were noted at small tumor burdens prior to a decline in food intake. Viable hepatocytes were isolated from 4 groups: non-tumor-bearing (NTB), small tumor burden [(STB) 3.5% total body weight (TBW)], moderate tumor burden [(MTB) 14% TBW], and large tumor burden [(LTB) 23% TBW]. As expected in NTB rats, hepatocytes produced significantly more glucose with 20 mM lactate than 20 mM alanine or than Hanks' balanced salt solution (HBSS) alone. Hepatocytes from STB rats demonstrated the same basic relationship for lactate, alanine, and HBSS, but they produced significantly more glucose from lactate and HBSS alone than NTB hepatocytes. With alanine as substrate, the rates of glucose production by hepatocytes were not affected by the presence or size of tumor. However, with lactate as substrate, hepatocytes from MTB and LTB rats produced progressively less glucose as tumor burden increased (r = -0.85, p less than .001), which may partly explain the reduction in blood glucose and elevation in blood lactate levels observed. Elevated gluconeogenesis in TB rats occurred early prior to a decline in food intake. The key precursor appeared to be lactate. The balance between glucagon and insulin appeared to promote the abnormal host carbohydrate metabolism observed.
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PMID:Gluconeogenesis in the tumor-influenced rat hepatocyte: importance of tumor burden, lactate, insulin, and glucagon. 331 83

Ten undernourished patients receiving total parenteral nutrition and undergoing major intestinal surgery were restarted on intravenous feeds identical to their pre-operative regimens within 24 h of their operation. Five, chosen at random, received post-operatively 1-2 units insulin/kg body weight/24 h with their feed, while the other five received the feed only. Pre-operatively, and 2 h after commencing their post-operative feeds, rates of whole-body protein synthesis and breakdown were measured over a 9-h period following intravenous injection of a single tracer dose of 15N-glycine by the ammonia and urea end-product methods. During these 9-h study periods measurements were also made of blood glucose, plasma insulin and glucagon, urinary ammonia, nitrogen, creatinine and 3-methylhistidine. Blood glucose and plasma insulin and glucagon concentrations rose post-operatively whether or not insulin was given, but the increment in insulin concentration was significantly greater when insulin was given. Apparent nitrogen balance was positive pre-operatively and became less so post-operatively whether insulin was given or not. Similarly, post-operative increments in urinary excretion of ammonia, creatinine and 3-methylhistidine were not altered by addition of insulin. Protein turnover, as estimated by the ammonia end-product method, tended to rise post-operatively, but there was no significant difference between the increases observed with or without insulin. The urea end-product method suggested that there was no change in whole-body protein turnover after surgery, whether or not insulin was given. This study does not support the clinical use of insulin as a means of modifying protein metabolic losses after major surgery.
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PMID:The effect of surgical trauma and insulin on whole-body protein turnover in parenterally-fed undernourished patients. 642 Mar 74

Patients with major injury or illness develop protein wasting, hypermetabolism, and hyperglycemia with increased glucose flux. To assess the role of elevated counterregulatory hormones in this response, we simultaneously infused cortisol (6 mg/m2 per h), glucagon (4 ng/kg per min), epinephrine (0.6 microgram/m2 per min), and norepinephrine (0.8 micrograms/m2 per min) for 72 h into five obese subjects receiving only intravenous glucose (150 g/d). Four obese subjects received cortisol alone under identical conditions. Combined infusion maintained plasma hormone elevations typical of severe stress for 3 d. This caused a sustained increase in plasma glucose (60-80%), glucose production (100%), and total glucose flux (40%), despite persistent hyperinsulinemia. In contrast, resting metabolic rate changed little (9% rise, P = NS). Urinary nitrogen excretion promptly doubled and remained increased by approximately 4 g/d, reflecting increased excretion of urea and ammonia. Virtually all plasma amino acids declined. The increment in nitrogen excretion was similar in three additional combined infusion studies performed in 3-d fasted subjects not receiving glucose. Cortisol alone produced a smaller glycemic response (20-25%), an initially smaller insulin response, and a delayed rise in nitrogen excretion. By day 3, however, daily nitrogen excretion was equal to the combined group as was the elevation in plasma insulin. Most plasma amino acids rose rather than fell. In both infusion protocols nitrogen wasting was accompanied by only modest increments in 3-methylhistidine excretion (approximately 20-30%) and no significant change in leucine flux. We conclude: (a) Prolonged elevations of multiple stress hormones cause persistent hyperglycemia, increased glucose turnover, and increased nitrogen loss; (b) The sustained nitrogen loss is no greater than that produced by cortisol alone; (c) Glucagon, epinephrine, and norepinephrine transiently augment cortisol-induced nitrogen loss and persistently accentuate hyperglycemia; (d) Counterregulatory hormones contribute to, but are probably not the sole mediators of the massive nitrogen loss, muscle proteolysis, and hypermetabolism seen in some clinical settings of severe stress.
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PMID:Role of counterregulatory hormones in the catabolic response to stress. 651 25

The rates of muscle protein breakdown, as estimated by the urinary excretion of 3-methylhistidine, were assessed in 30 cirrhotics and 15 controls on a strictly controlled diet. 3-Methylhistidine excretion was increased in cirrhotics irrespective of the etiology of the disease, and correlated with basal glucagon levels and with the insulin/glucagon ratio. In nine cirrhotics and nine age- and sex-matched controls, similar correlations were found between 3-methylhistidine and the areas under 24-hr glucagon or insulin/glucagon curves. A larger amount of 3-methylhistidine was excreted during the nighttime than during the daytime, when glucagon secretion was suppressed and the insulin/glucagon ratio was increased. It is concluded that muscle protein catabolism is increased in cirrhotics, possibly as a result of hyperglucagonemia or the reduced insulin/glucagon ratio. These data agree with the clinical observation of a progressive reduction in lean body mass which becomes evident in an advanced stage of the disease.
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PMID:Muscle protein breakdown in liver cirrhosis and the role of altered carbohydrate metabolism. 702 4

An anabolic stimulus is needed in addition to conventional nutritional support in the catabolic "flow" phase of severe trauma. One promising therapy appears to be rhGH infusion which has direct as well as hormonal mediated substrate effects. We investigated on a whole-body level, the basic metabolic effects of trauma within 48-60 h after injury in 20 severely injured (injury severity score [ISS] = 31 +/- 2), highly catabolic (N loss = 19 +/- 2 g/d), hypermetabolic (resting energy expenditure [REE] = 141 +/- 5% basal energy expenditure [BEE]), adult (age 46 +/- 5 y) multiple-trauma victims, before starting nutrition therapy and its modification after 1 wk of rhGH supplementation with TPN (1.1 x REE calories, 250 mg N.kg-1.d-1). Group H (n = 10) randomly received at 8:00 a.m. on a daily basis rhGH (0.15 mg.kg-1.d-1) and Group C (n = 10) received the vehicle of infusion. Protein metabolism (turnover, synthesis and breakdown rates, and N balance); glucose kinetics (production, oxidation, and recycling); lipid metabolism, (lipolysis and fat oxidation rates), daily metabolic and fuel substrate oxidation rate (indirect calorimetry); and plasma levels of hormones, substrates, and amino acids were quantified. In group H compared to group C: N balance is less negative (-41 +/- 18 vs -121 +/- 19 mg N.kg-1.d-1, P = 0.001); whole body protein synthesis rate is 28 +/- 2% (P = 0.05) higher; protein synthesis efficiency is higher (62 +/- 2% vs 48 +/- 3%, P = 0.010); plasma glucose level is significantly elevated (256 +/- 25 vs 202 +/- 17 mg/dL, P = 0.05) without affecting hepatic glucose output (1.51 +/- 0.20 vs 1.56 +/- 0.6 mg N.kg-1.min-1), glucose oxidation and recycling rates; significantly enhanced rate of lipolysis (P = 0.006) and free fatty acid reesterification (P = 0.05); significantly elevated plasma levels of anabolic GH, IGF-1, IGFBP-3, and insulin; trauma induced counter-regulatory hormone (cortisol, glucagon, catecholamines) levels are not altered; trauma induced hypoaminoacidemia is normalized (P < 0.05) and 3-methylhistidine excretion is significantly low (P < 0.001). Improved plasma IGF-1 levels in Group H compared with Group C account for protein anabolic effects of adjuvant rhGH and may be helpful in promoting tissue repair and early recovery. Skeletal muscle protein is spared by rhGH resulting in the stimulation of visceral protein breakdown. The hyperglycemic, hyperinsulinemia observed during rhGH supplementation may be due to defective nonoxidative glucose disposal, as well as inhibition of glucose transport activity into tissue cells. The simultaneous operation of increased lipolytic and reesterification processes may allow the adipocyte to respond rapidly to changes in peripheral metabolic fuel requirements during injury. This integral approach helps us to better understand the mechanism of the metabolic effects of rhGH.
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PMID:Integrated nutritional, hormonal, and metabolic effects of recombinant human growth hormone (rhGH) supplementation in trauma patients. 897 4


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