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)

To determine if exercise intolerance and fatigue in chronic heart failure could be exacerbated by an abnormal metabolic response to exercise, we studied 12 patients with stable chronic heart failure and 12 normal volunteers during symptom-limited maximal treadmill exercise. Peak VO2 was 17.2 (15.1-19.2) ml.kg-1 x min-1 in patients and 29.9 (26.3-33.5) in controls (mean and 95% confidence intervals; P < 0.0001, t-test). Overall, levels in peripheral venous blood of glucose, glycerol and free fatty acids were greater in patients, although the differences became less marked with increasing exercise intensity. Noradrenaline was elevated in patients at rest, but the peak exercise response was similar to controls. Responses of adrenaline, insulin and glucagon were similar in both groups. We conclude that depletion of the levels of circulating substrates is not contributory to exercise intolerance and fatigue in chronic heart failure. Greater levels of glycerol and free fatty acids may be mediated by excess sympathetic nervous system activity, reflected in elevated noradrenaline levels.
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PMID:Metabolic responses to graded exercise in chronic heart failure. 829 29

Nineteen bulimic women and 22 age-matched controls were randomly assigned to receive 25 g of glucose or a placebo injection under double-blind conditions. Blood samples of glucose, insulin, and glucagon, and psychometric assessments of mood and food cravings were obtained 10 min before, and 0, 5, 10, 20, 30, 45, and 60 min after injection. Blood levels of the large neutral amino acids (LNAAs) tryptophan, tyrosine, leucine, valine, phenylalanine, and leucine were determined at 10 min before and 60 min after the injection. Bulimic subjects were found to report more symptoms of distressed mood throughout the entire monitoring period than controls. Five minutes following glucose ingestion the self-reports of depression, fatigue, anxiety, and bewilderment rose to a level among the bulimic subjects that was above that at baseline, and was higher than that of bulimia nervosa (BN) subjects receiving placebo. No comparable change in mood was observed among controls. Blood glucose levels were correlated with mood in the bulimic group, but not in controls. In addition, the glucose injection induced a heightened urge to binge in the bulimic group (compared to placebo at 10 and 60 min), whereas reducing food cravings (for sweets) in the controls (at 5 min). When collapsed across time and injection condition, the blood glucose level of bulimics was lower than that of controls. There were no differences in insulin response between the groups. The bulimic group was found to have lower baseline levels of blood tryptophan, whereas no differences in the tryptophan/LNAA ratio were observed either at baseline or following glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A double-blind placebo-controlled glucose challenge in bulimia nervosa: psychological effects. 844 64

A 65-yr-old woman presented for evaluation of a pancreatic mass. She had been suffering from severe constitutional symptoms for 18 months; those symptoms included weight loss, increasing fatigue, night sweats, and recurrent fever attacks up to 40 degrees C. Later, bluish subcutaneous nodules developed on her lower limbs. Laboratory tests yielded signs of chronic inflammation and impaired glucose tolerance with elevated serum insulin and glucagon concentrations. Skin biopsy revealed lobular panniculitis. Ultrasonography and a CT scan demonstrated enlargement of the pancreas, and endoscopic retrograde pancreaticography disclosed displacement and stenosis of the main pancreatic duct. The patient was referred for explorative laparotomy, which was highly suggestive of a malignant pancreatic tumor. However, histological examination of the resected pancreatic and peripancreatic mass revealed tuberculous pancreatitis. This form of isolated tuberculous pancreatitis, associated with lobular panniculitis and laboratory features consistent with a tumor of the endocrine pancreas, has not been reported previously. Active tuberculosis should be a leading differential diagnosis in a patient with an enlarged pancreas when the usual diagnostic reasoning does not yield conclusive results.
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PMID:Isolated tuberculosis of the pancreas masquerading as a pancreatic mass. 854 May 23

Muscle phosphofructokinase deficiency (PFKD) is characterized by exercise intolerance due to the enzymatic block in muscle glycolysis. Glucose infusion increases exertional fatigue in these patients, probably by decreasing the availability of free fatty acids (FFA) and ketones, which play a crucial role in ATP production during exercise in PFKD. This suggests that a lower than normal hepatic glucose production would be appropriate during exercise in PFKD. To investigate glucoregulation in PFKD, we measured glucose turnover and hormonal and metabolic responses to 20 minutes of cycle exercise at near maximal effort in three patients with PFKD and in healthy matched controls studied at the same absolute (A, 15 to 30 Watts) and relative (R, 35 to 80 Watts, matched heart rates) work load as the patients. During exercise, mean glucose production was higher in all patients versus controls (30 +/- 4 versus A: 18 +/- 2 and R: 20 +/- 1 mumol.min-1.kg-1). Mean glucose utilization during exercise was similar in patients and controls working at the same relative work load and higher than in controls at the low work load. Exercise-induced increases in arterialized blood were higher in all patients for glucose, FFA, growth hormone, glucagon, and norepinephrine. Plasma alanine and lactate always decreased during exercise in patients and consistently increased in controls. In conclusion, an enhanced neuroendocrine response and a paradoxically exaggerated mobilization of glucose occurs during exercise in PFKD. The responses are probably initiated by neural feedback elicited by disturbances in local muscle metabolism. The responses promote delivery of oxidizable fat to muscle, but at the expense of accumulation and futile cycling of glucose.
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PMID:Paradoxically enhanced glucose production during exercise in humans with blocked glycolysis caused by muscle phosphofructokinase deficiency. 879 77

It is generally recognized that a decrease in carbohydrate availability can lead to the development of fatigue during prolonged exercise in humans. Administration of glucose or other carbohydrates before or during exercise has been shown to postpone fatigue, conserve muscle glycogen and improve performance. Carbohydrates can be categorised according to their ability to increase blood glucose concentration (known as glycaemic index) and by the extent they stimulate the release of insulin. The glycaemic index is reflected in the rate at which consumed carbohydrate is made available in the blood. Glucose is the only type of carbohydrate that can readily be oxidised by skeletal muscle for energy production. Gastric emptying is the primary factor limiting the rate of carbohydrate delivery to the blood and therefore influences the utilisation of exogenous carbohydrate ingested before or during exercise. Various methods have been used to assess the oxidation of exogenous carbohydrates during exercise. Peak rates of CHO oxidation during exercise have been reported between 0.4 and 1.0 g/min, and the rates of oxidation do not appear to be influenced to a major extent by the use of multiple drinking schedule in comparison with a single bolus schedule. Previous studies also suggest that the ingestion of fructose during exercise does not offer any additional benefits over ingestion of glucose or glucose polymer solutions of similar concentration. The hormones insulin, glucagon and adrenaline together with cortisol and growth hormone play key roles in the regulation of carbohydrate metabolism during exercise. Ingestion of moderately concentrated carbohydrate solutions (4-8%) enhances prolonged exercise performance and is appropriate for optimising energy and fluid delivery without causing adverse effects. The ergogenic effects of carbohydrate ingestion on performance during intermittent exercise such as competitive sports are less well established, although the evidence to date suggests diminished performance when carbohydrate are limiting.
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PMID:Exogenous carbohydrate utilisation: effects on metabolism and exercise performance. 940 48

Low muscle glycogen at the beginning of exercise may adversely affect performance, increase protein degradation and contribute to the onset of fatigue. As horses are sometimes required to compete on consecutive days both in racing and endurance types of competition, optimal muscle glycogen repletion may improve performance on the day following a race day. The purpose of this experiment was to study the effects of fat supplementation on repletion of muscle glycogen. Twelve Finnhorses performed an exercise test on a treadmill, and 2 and 4 h later they received hay and concentrate (Trial A). Two weeks later these horses performed the same exercise test and were fed the same diet supplemented with either 1000 g of carbohydrate or 400 g of vegetable oil (Trial B). A third trial (Trial C) was 3 weeks later, identical to Trial B, except that the fat group had already been adapted to dietary fat for 3 weeks. Blood samples were analysed for lactate, glucose, glycerol, triglycerides, NEFA, cholesterol, beta-OH-butyrate, insulin and glucagon and muscle samples were analysed for glycogen and triglycerides. The results indicate that in horses not adapted to fat feeding, fat supplementation slows the rate of muscle glycogen repletion, and that after an adaptation period, fat supplementation does not alter the rate of muscle glycogen repletion compared to the rate with a normal diet.
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PMID:Effect of a post exercise fat-supplemented diet on muscle glycogen repletion. 1065 6

The effects of three isoenergetic diets on metabolic and appetite responses to prolonged intermittent walking were investigated. Eight men undertook three 450-min walks at intensities varying between 25-30 and 50-55% of maximal O2 uptake. In a balanced design, the subjects were given breakfast, snacks, and lunch containing total carbohydrate (CHO), protein (P), and fat (F) in the following amounts (g/70 kg body mass): mixed diet, 302 CHO, 50 P, 84 F; high-CHO diet, 438 CHO, 46 P, 35 F; high-fat diet, 63 CHO, 44 P, 196 F. Substrate balance was calculated by indirect calorimetry over the 450-min exercise period. Blood samples were taken before exercise and every 45 min during the exercise period. The high-fat diet resulted in a negative total CHO balance (-140 +/- 1 g) and a lower negative fat balance (-110 +/- 33 g) than the other two diets (P < 0.05). Plasma glucagon, nonesterified fatty acids, glycerol, and 3-hydroxybutyrate were higher with the high-fat diet (P < 0.05 vs. high CHO), whereas plasma insulin was lower after high fat (P < 0.05 vs. mixed and high CHO). Subjective ratings of fatigue and appetite showed no differences between the three trials. Although diet influenced the degree of total CHO and fat oxidation, fat was the main source of energy in all trials.
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PMID:Metabolic and appetite responses to prolonged walking under three isoenergetic diets. 1196 Sep 58

Four cases of asthma (one adult, three children) developing acute adrenal crisis after introduction of high-dose inhaled fluticasone proprionate are presented. The three children, aged 7-9 yrs, had been prescribed inhaled fluticasone, dosage 500-2,000 microg x day(-1) and duration 5 months-5 yrs. All presented with convulsions due to hypoglycaemia (blood glucose 1.3-1.8 mM). The fourth case was a male of 33 yrs with difficult-to-control asthma and had been taking fluticasone propionate 1,000-2,000 microg x day(-1) for 3 yrs. He presented with fatigue, lethargy, nausea and postural hypotension. Acute adrenal crisis in each case was confirmed by investigations which included measurement of acute phase cortisol levels, short and long Synacthen stimulation tests and glucagon stimulation tests. Other cases of hypthoalamic-pituitary-adrenal axis suppression were excluded.
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PMID:Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate. 1210 82

In several species, physical conditioning (training) provokes a large shift in substrate utilisation during submaximal exercise. Few studies in horses have quantitatively examined these effects. Therefore, the effects of exercise training on plasma glucose kinetics during submaximal exercise were examined in 7 horses (5 Thoroughbred, 2 Standardbred; age 3-9 years) that had been paddock-rested for at least 6 months. Two days after determination of maximum aerobic capacity (VO2max), horses ran on a treadmill (4 degree incline) at 55% of VO2max (UT) for 60 min or until fatigue and then completed 6 weeks of moderate-intensity training on a treadmill (5 days/week). Following training and a second VO2max test, the horses completed exercise trials at the same absolute (ABS) and relative (REL) workload in random order, with at least 3 days between tests. After training, VO2max had increased (P<0.05) by 14.9% (mean +/- s.e. pretraining 118.4 +/- 7.4 ml/kg bwt/min; post-training 136.1 +/- 7.8 ml/kg bwt/min). Mean exercise duration was longer (P<0.05) in the ABS trial (57 +/- 1.9 min) than in the UT (46 +/- 3.9 min) and REL (49 +/- 4.6 min) trials. Plasma glucose concentration increased during exercise, and was lower (P<0.05) in ABS than in UT and REL at the end of exercise. Mean glucose rate of appearance (Ra) and disappearance (Rd) were 22 and 21% lower (P<0.05), respectively, in ABS than in UT, but mean glucose Ra and Rd did not differ between the UT and REL trials. Exercise-induced changes in glucagon, epinephrine and norepinephrine were blunted (P<0.05) in ABS, but not REL, when compared to UT. It is concluded that 6 weeks of moderate-intensity training results in a decrease in glucose flux during submaximal exercise at the same absolute, but not relative, workload. The training-induced decrease in glucose flux may, in part, be due to altered plasma concentrations of the major glucoregulatory hormones.
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PMID:Training-induced alterations in glucose metabolism during moderate-intensity exercise. 1240 54

Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory. Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform. All documented symptoms of CFS are explained by vasoactive neuropeptide compromise, namely fatigue and nervous system dysfunction through impaired acetylcholine activity, myalgia through nitric oxide and endogenous opioid dysfunction, chemical sensitivity through peroxynitrite and adenosine dysfunction, and immunological disturbance through changes in immune modulation. Perverse immunological memory established against these substances or their receptors may be the reason for the protracted nature of this condition. The novel status of these substances together with their extremely small concentrations in blood and tissues means that clinical research into them is still in its infancy. A biologically plausible theory of CFS causation associated with vasoactive neuropeptide dysfunction would promote a coherent and systematic approach to research into this and other possibly associated disabling conditions.
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PMID:Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry? 1508 83


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