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)

A juvenile-type diabetic patient of five years standing presented with a mononeuritis and gave a history of painful muscle swelling induced by exertion. Failure of the blood lactate to rise during ischaemic exercise and a normal blood glucose rise following intravenous glucagon confirmed the clinical diagnosis of muscle glycogenosis. The association of diabetes and McArdle's Syndrome has not previously been documented. An ulnar nerve palsy, which persisted for many months, followed the ischaemic exercise test possibly due to compression by muscular swelling, but may have been exacerbated by the co-existing diabetes.
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PMID:Neuropathy in a patient with McArdle's syndrome and diabetes mellitus. 27 Apr 56

Each of 12 types of glycogen storage disease (GSD O-XI) is delineated by clinical, biochemical and histologic features that allow its identification in future patients. GSD II occurs in 2 forms that are not both encountered in the same family. GSD IIa is the infantile fatal form with cardiomegaly, increased cardiac glycogen concentration and cardiac failure; GSD IIb is the adult form with clinically normal heart and normal cardiac glycogen concentration. Nonetheless, the heart muscle of both forms is equally deficient in acid alpha-glucosidase activity, and this raises questions as to the latter's role in the pathophysiology of GSD II. The appearance of hepatocytes in GSD IIa becomes normal after the administration of alpha-glucosidase. Using electron microscopy of uncultured amniotic fluid cells, the prenatal diagnosis of GSD IIa is feasible within one day after the amniocentesis. GSD VI and IX are instances of benign hepatomegaly except when GSD IX and III occur in the same child; one such patient died suddenly at home. There are 2 modes of inheritance in GSD IX: one (GSD IXa) is autosomal recessive, the other one (GSD IXb) is X-linked recessive. In either form the Km of the remaining liver phosphorylase kinase is normal. Both forms of GSD IX have the normal blood sugar response to glucagon, whereas GSD VI does not. Equally, the glucagon tolerance curve is flat in GSD XI although in vitro activity of glycolytic enzymes is normal. The in vivo administration of glucagon in GSD XI is followed by the normal increase of both urinary 3'5'-AMP and hepatic phosphorylase activity. GSD V may have increased activity of muscle phosphorylase kinase. Deficiencies of debrancher, liver phosphorylase and liver phosphorylase kinase can occur singly or in combination. Before any novel treatment of GSD is initiated, one should obtain tissue for the biochemical determination of the exact type of GSD. This is so because the clinical signs may not indicate the type with the necessary precision, and because some types are compatible with normal life and thus may not require therapy, especially if the latter is unproved and potentially dangerous.
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PMID:Glycogen storage diseases. 78 7

Experimental therapies for McArdle's disease have been directed toward increasing substrate availability to exercising muscle. Such therapies to date have proven largely unsuccessful. These include administration of isoproterenol to increase blood flow, glucagon treatment to elevate serum glucose and increased dietary fat intake. Each of these therapies also results in greater levels of unesterified fatty acids in blood. More recently, a high protein diet is suggested to provide increased amounts of amino acids which would be available as fuel sources. We hypothesize that the absence of myophosphorylase in McArdle's disease creates an imbalance between the enzymes of the redox systems that control the generation, propagation and inactivation of free radicals. This occurs because muscle cells are forced to rely more heavily on fatty acid oxidation. The resulting free radical damage to cellular components disrupts metabolic control and increases the permeability of membranes. Elevated levels of Ca2+ in the sarcoplasm activate proteases, phospholipases and other catabolic enzymes initiating muscle fatigue and cramping. Lipid peroxidation is a consequence of normal muscle activity and may occur unchecked in individuals with McArdle's disease. Continued muscle activity in the absence of a favorable nutritional environment may promote the progression of the disease by increasing susceptibility to oxidative stress.
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PMID:The role of lipid peroxidation in McArdle's disease: applications for treatment of other myopathies. 146 Nov 77

Glucagon has been reported to improve exercise tolerance in some patients with myophosphorylase deficiency (McArdle's disease) but a placebo effect was not excluded in previous trials. A single-blind controlled trial of glucagon in a patient with myophosphorylase deficiency is described. Although an improved exercise endurance of the forearm muscles was demonstrated with both short-acting and depot-glucagon, this was not statistically significant when compared with placebo or no treatment.
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PMID:Depot-glucagon in the treatment of McArdle's disease. 386 41

Pretreatment with glucagon relieved patients with McArdle disease from muscular symptoms during exercise and enhanced exercise performance, though it did not produce any improvement in patients with Tarui disease. The difference in glucagon effect between the two diseases was clearly demonstrated in the bicycle ergometer exercise tests. In addition, the semi-ischemic forearm exercise tests performed after glucagon injection showed that increased lactate production was significantly induced by exercise in McArdle disease, but it was not the case in Tarui disease. In McArdle disease, the augmentation in exercise-induced lactate production was also observed after administration of glucose, or glucose plus insulin, but it was neither observed after administration of insulin alone nor after arginine or epinephrine administration. These findings suggest that the beneficial effect of glucagon in McArdle disease is due to the enhanced utilization of circulating glucose through the muscular glycolytic pathway realized in the coexistence of hyperglycemia and hyperinsulinemia.
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PMID:A comparative study on glucagon effect between McArdle disease and Tarui disease. 624 22

A 26-year-old girl with muscle phosphorylase deficiency had exercise intolerance and experienced an occasional "second wind" phenomenon. Muscle glycogen concentration was about three times the normal level, whereas each glycolytic intermediate below the phosphorylase step was equivalent to only 10% of a normal level. Semi-ischemic forearm exercise tests disclosed no elevation of the venous lactate or pyruvate level, but they showed remarkable increases of serum creatine kinase and ammonia. Glucagon administration markedly augmented exercise tolerance. Forearm exercise after glucagon injection significantly increased venous lactate. Thus, the beneficial effect of glucagon is attributable to blood glucose utilization by muscle.
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PMID:Metabolic basis of improved exercise tolerance: muscle phosphorylase deficiency after glucagon administration. 659 2

Typical signs and findings of McArdle's disease were noted in a 27-year-old women. Echocardiographically there was impaired myocardial function. Subcutaneous injection of 2 mg depot-glucagon increased blood sugar levels with objective improvement of muscular function. This is suggested as a practical method of treatment for anticipated increase in muscular stress.
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PMID:[McArdle's disease: therapeutic use of depot-glucagon]. 695 45

We reported a 29-year-old woman with McArdle's disease accompanied with insulin resistance. The patient was referred to our hospital because of muscle tenderness, swelling and weakness of lower extremities, and elevated serum CK level. Ischemic forearm exercise test showed no elevation in serum lactate and pyruvate levels. Muscle biopsy revealed significant reduction in phosphorylase activity both histochemically and biochemically. Pre-administration of glucagon had no effect on serum lactate and pyruvate levels after ischemic forearm exercise test while serum glucose elevated. The glucose clamp test confirmed insulin resistance. There was no reduction in number of insulin receptor or activity of tyrosine kinase. Her bodyweight was 78.4 kg and body mass index (BMI) was high as 32.0. Her obesity might be a causative factor of insulin resistance.
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PMID:[McArdle's disease with insulin resistance caused by obesity]. 1266 Nov 10

Background McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria rhabdomyolysis and acute renal failure. This is an update of a review first published in 2004.Objectives To review systematically the evidence from randomised controlled trials (RCTs) of pharmacological or nutritional treatments for improving exercise performance and quality of life in McArdle disease.Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE on 11 August 2014.Selection criteria We included RCTs (including cross-over studies) and quasi-RCTs. We included unblinded open trials and individual patient studies in the discussion. Interventions included any pharmacological agent or nutritional supplement. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO2) max, walking speed, muscle force or power and fatigability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase and a reduction in the frequency of myoglobinuria), subjective measures (including quality of life scores and indices of disability) and serious adverse events.Data collection and analysis Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. Two review authors independently assessed the risk of bias of relevant studies, with comments from a third author. Two authors extracted data onto a specially designed form.Main results We identified 31 studies, and 13 fulfilled the criteria for inclusion. We described trials that were not eligible for the review in the Discussion. The included studies involved a total of 85 participants, but the number in each individual trial was small; the largest treatment trial included 19 participants and the smallest study included only one participant. There was no benefit with: D-ribose,glucagon, verapamil, vitamin B6, branched chain amino acids, dantrolene sodium, and high-dose creatine. Minimal subjective benefit was found with low dose creatine and ramipril only for patients with a polymorphism known as the D/Dangiotens in converting enzyme(ACE) phenotype. A carbohydrate-rich diet resulted in better exercise performance compared with a protein-rich diet. Two studies of oral sucrose given at different times and in different amounts before exercise showed an improvement in exercise performance. Four studies reported adverse effects. Oral ribose caused diarrhoea and symptoms suggestive of hypoglycaemia including light-headedness and hunger. In one study, branched chain amino acids caused a deterioration of functional outcomes. Dantrolene was reported to cause a number of adverse effects including tiredness, somnolence, dizziness and muscle weakness. Low dose creatine (60 mg/kg/day) did not cause side-effects but high-dose creatine (150 mg/kg/day) worsened the symptoms of myalgia.Authors' conclusions Although there was low quality evidence of improvement in some parameters with creatine, oral sucrose, ramipril and a carbohydrate rich diet, none was sufficiently strong to indicate significant clinical benefit.
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PMID:Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V). 2115 53