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)

Five patients, 4 men and 1 woman, had adult-onset and slowly progressive weakness. There was distal wasting in 2, hepatomegaly in 3, and congestive heart failure in 2. Electromyography showed a mixed pattern with abundant fibrillations. Serum creatine phosphokinase was increased 5- to 45-fold. Blood glucose failed to respond to epinephrine or glucagon, and venous lactate did not rise after ischemic exercise. Muscle biopsy showed vacuolar myopathy affecting both fiber types. By electron microscopy the vacuoles corresponded to large pools of glycogen not limited by a membrane. Glycogen concentration was 3 to 5 times normal in muscle and 7 to 21 times normal in erythrocytes. In the presence of iodine, muscle glycogen showed a spectrum characteristic of phosphorylase-limit-dextrin. Debrancher activity was measured by a spectrophotometric assay and by a radioactive reverse reaction. The activity was lacking in muscle and erythrocytes of 4 patients according to both assays; in 1 patient the reverse reaction was not impaired. Though previously reported in only 5 patients, debrancher deficiency myopathy may not be rare and should be considered in the differential diagnosis of adult-onset hereditary myopathies.
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PMID:Debrancher deficiency: neuromuscular disorder in 5 adults. 28 18

To determine if pancreatic glucoregulatory hormones can be implicated in the glucose fall of pregnancy, we have measured plasma immunoreactive insulin and glucagon (IRI and IRG) in rats. Fed rats in midgestation show a rise in IRI without a corresponding increase in IRG. In late gestation, IRG rises significantly, but only enough to keep pace with a further rise in IRI. On a molar basis, IRI remains the predominant hormone despite a marked fall in blood glucose. After a 48-h fast IRI falls to comparably low levels in pregnant and virgin rats. A small rise in IRG is seen in virgin but not in pregnant rats despite frank hypoglycemia in the latter. Thus, IRG secretion in pregnancy is diminished relative to IRI in the fed state and fails to increase in the fasted state despite the stimulus of a lower glucose in both instances. To evaluate IRG secretory reserve, the IRG response to i.v. alanine was assessed in late gestation. In fed rats a greater IRG increase is seen in pregnancy; after fasting no difference is seen between pregnant and virgin rats. These results preclude an absolute deficiency in glucagon secretion. Pancreas hormone stores were alos measured in an effort to explain the altered secretory state. We find reciprocal changes in IRI and IRG content favoring IRG in midgestation and IRI in late gestation. Thus, pancreas hormone storage is altered in pregnancy but does not account for the changes in hormone secretion. Rather, pregnancy exerts an effect on the islet secretory process itself. Release of IRI is enhanced relative to IRG regardless of the blood sugar level. These observations suggest that in the pregnant rat circulating levels of insulin and glucagon may act to limit hepatic glucose output. Available evidence from the literature supports the concept of restrained glucose production. It is proposed that a lower blood glucose production. It is proposed that a lower blood glucose in rat pregnancy may be a lesser liability teleologically than would be the obligate nitrogen wasting which accompanies gluconeogenesis.
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PMID:Plasma glucagon and insulin in rat pregnancy. Roles in glucose homeostasis. 110 77

Severe burn injury elicits the release of catabolic hormones that contribute to negative nitrogen balance, protein wasting, and impaired wound healing. Previous studies have shown that burn patients receiving recombinant human growth hormone (rhGH) therapy have an increase in the rate of skin donor site healing and a shorter hospital stay. The mechanism by which rhGH exerts its effects, however, is not clearly understood. This study examines the effects of rhGH on circulating levels of catabolic hormones and nonesterified fatty acids in pediatric burn patients. Patients with greater than 40% total body surface area burn were randomly assigned to receive placebo (n = 8) or 0.2 mg/kg/day rhGH (n = 6) throughout their hospitalization. All patients had early morning blood samples assessed for catecholamines (CAT), cortisol, insulin, glucagon, and free fatty acid (FFA) levels during a period of hypermetabolism. No differences could be demonstrated in age, burn size, postburn day of evaluation, resting energy expenditure per kilogram, respiratory rate, heart rate, respiratory quotient, serum cortisol, and serum glucose between placebo- and rhGH-treated patients. The rhGH-treated group did show a significant elevation (p less than 0.05) in insulin-like growth factor-1 (55.9 +/- 14.5 vs. 168 +/- 23.7 mU/mL), total catecholamines (1,817 +/- 177 vs. 1,117 +/- 137 pg/mL), norepinephrine (1,257 +/- 121 vs. 867 +/- 113 pg/mL), epinephrine (385 +/- 175 vs. 147 +/- 36 pg/mL), insulin (32.8 +/- 3.3 vs. 25.0 +/- 3.0 mU/mL), glucagon (215 +/- 18 vs. 158 +/- 22 pg/mL), and free fatty acids (0.74 +/- 0.01 vs. 0.59 +/- 0.04 mEq/L) compared with the placebo group (data expressed as mean +/- SE).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of recombinant human growth hormone on catabolic hormones and free fatty acids following thermal injury. 161 29

Metabolic changes in rats fed a low protein diet were investigated during 3 weeks after weaning using lactalbumin (LP) as dietary protein source. The energy intake was higher and the weight gain lower in rats fed the low protein diet (6%, LP group) than in control rats (13% lactalbumin, C group). Low protein diet induced no changes in plasma glucose, free fatty acids, or triacylglycerol concentrations; however, plasma protein and urea concentrations were lower in LP than in C rats. Plasma free T3 was higher in LP than in C rats (+38%, day 21) and insulin progressively decreased during the experimental period (-56%, day 21) without change in glucagon. Liver glycogen and triacylglycerol concentrations (+40% and +180%, respectively, day 21), and cytosolic and mitochondrial redox states increased (+100% and +100%, day 21), and protein concentration was decreased (-15%, day 21). Pyruvate kinase (PK) and malic enzyme activities were higher in LP than in C rats throughout the experiment (+80% and +210%, respectively, day 21), and glucose-6-phosphate dehydrogenase (G6PDH) activity progressively decreased (-65%, day 21). Phosphoenolpyruvate carboxykinase (PEPCK) activity increased after 2 weeks on a LP diet (+35%, day 21) and fatty acid synthetase (FAS) activity increased only during the first week on the diet (+100%, day 7). Such hormonal and metabolic changes appeared to be associated with the development of a futile energy-wasting cycle between pyruvate and phosphoenolpyruvate.
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PMID:Metabolic changes in rats fed a low protein diet during post-weaning growth. 219 92

To determine the role insulin resistance may play in the catabolic effect of high-dose prednisone therapy, healthy volunteers were studied on four occasions with the hormone-clamp technique at two insulin infusion rates. Subjects were studied after 5 days of prednisone (60 mg/day) or no steroid treatment and were infused with somatostatin, glucagon, growth hormone, [3H]glucose, [14C]leucine, and insulin (0.1 or 0.2 mU.kg-1.min-1). At each rate of insulin infusion, the rate of leucine oxidation was increased (P less than .001) after steroid treatment. Leucine flux, an indicator of whole-body proteolysis, was similar in the presence or absence of steroid treatment (2.26 +/- 0.08 vs. 2.13 +/- 0.04 mumol.kg-1.min-1, respectively) at the lower rate of insulin infusion but was higher during steroid treatment (2.18 +/- 0.06 vs. 1.84 +/- 0.13 mumol.kg-1.min-1) at the 0.2-mU.kg-1.min-1 insulin infusion. Steroid pretreatment had no significant effect on the nonoxidative rates of leucine disappearance. These data provide strong evidence that the protein wasting associated with glucocorticosteroid therapy is in part the result of steroid-induced resistance to the antiproteolytic effect of insulin and an increase in the oxidation (and thus wasting) of one essential amino acid, leucine.
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PMID:Contribution of insulin resistance to catabolic effect of prednisone on leucine metabolism in humans. 257 41

We report a case of a 17 year old sports woman, who had a ventricular fibrillation episode with cardiogenic shock during endonasal anaesthesia containing epinephrine. She was so transferred to our department (in shock): the 2-D echo showed biventricular hypokinesia without dilatation (LVEF less than 25%). Endomyocardial biopsy performed 5 days later showed active lymphocyte myocarditis with interstitial fibrosis. There were serum antibodies anti-Echo 9 and Coxsackie B 1, 2, 3. Immunoassay, urinary catecholamines and glucagon test were normal. The clinical picture was resolved within 15 days using intravenous isoprenaline and/or dopamine initially followed by oral diuretics and digoxin; the therapy was broke off at the time of discharge. We believe that the vasoconstriction and/or the oxygen wasting effect caused by epinephrine revealed latent myocarditis which had not been shown up even by intensive physical training.
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PMID:[Acute latent myocarditis appearing with ventricular fibrillation after intranasal administration of adrenaline. Description of a case]. 260 90

Tumor necrosis factor (TNF) has been implicated in the toxic manifestations of overwhelming bacterial infection and in the tissue wasting that often accompanies prolonged infections and malignancy. We have examined a possible role of TNF in the early metabolic alterations following acute tissue injury or sepsis. Recombinant human TNF stimulated rat liver amino acid uptake up to 5-fold in vivo and there was a concomitant increase in plasma glucagon. In vitro TNF had no direct effect on hepatocyte amino acid uptake, but it markedly enhanced the stimulation of amino acid transport by glucagon, without an alteration in binding of glucagon to hepatocytes. This permissive effect of TNF on glucagon action represents an interrelationship between the immune and endocrine systems, and it may help to explain the mechanism of hormonal regulation of both the anabolic and catabolic responses to acute injury.
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PMID:Modulation of endogenous hormone action by recombinant human tumor necrosis factor. 282 98

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

We describe two siblings with distal myopathy with rimmed vacuoles, who died suddenly presumably due to fatal arrhythmia. Case 1. A 26-year-old man with a 4 year-history of progressive muscle weakness and wasting was hospitalized in April, 1989. The family history showed that his younger brother had the same disease, but his parents, not consanguineous, and other family members had no neuromuscular diseases. On admission, neurologic examination showed muscle weakness and atrophy in the distal portions of four extremities. No myotonia or fasciculation was present. The deep tendon reflexes were absent except diminished bilateral PTR. Sensation and co-ordination were normal. The creatinine kinase (CK) level was moderately elevated to 691 IU/l, and the aldolase mildly to 6.9 IU/l. Normal laboratory values included serum electrolytes, glucose and thyroid function study. An ischemic forearm exercise test revealed a normal rise in serum lactate and pyruvate concentrations. The glucose response after glucagon was normal in the fasting state. An electrocardiogram and chest film were normal. An electromyogram revealed myopathic changes with mild neuropathic changes, including positive sharp waves and fibrillation potentials at rest. The muscle biopsy specimen from the left anterior tibial muscle showed scattered fibers with rimmed vacuoles and moderate variation in fiber size. Neither fiber necrosis nor inflammatory cellular infiltration was seen. Regenerating fiber was not present. An electron microscopic examination showed numerous lamellar bodies of various size. Nerve biopsy was normal. He was diagnosed as having distal myopathy with rimmed vacuoles. Muscle weakness progressed gradually over the next two years, but his general condition was good. He asked to receive the corticosteroid therapy, and rehospitalized.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Distal myopathy with rimmed vacuoles and sudden death--report of two siblings]. 826 2

Cancer and its therapies frequently produce anorexia and cachexia. In this study, the acute (3 days) and chronic (4 wks) nutrition-related effects of cancer therapy with recombinant human tumor necrosis factor (rHuTNF) were investigated and described. Nutritional status, as measured by body weight and body composition (body fat and lean-to-fat ratio) with use of bioelectrical impedance, did not appear to deteriorate. None of the serum lipids changed significantly, but triglycerides did rise modestly over four weeks of therapy. Glucose and the peptide hormones (insulin, C-peptide, glucagon, and pancreatic polypeptide) thought to affect appetite did not change with rHuTNF therapy. Therefore, although TNF is thought to contribute to wasting in animal models, it had no negative effect on nutritional status in our small sample. The lack of adverse effect noted in this study is possibly due to the low dose level of rHuTNF or to adaptation.
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PMID:Lack of significant changes in nutrition-related parameters with tumor necrosis factor treatment of cancer. 834 74


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