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)

Acidic phospholipids play a critical role in the hormone activation of adenylate cyclase. Solubilized myocardial adenylate cyclase is unresponsive to glucagon and the catecholamines, two of the hormones which activate the membrane-bound enzyme. Phosphatidylserine, purified from bovine brain restored glucagon responsiveness of the solubilized adenylate cyclase. Monophosphatidylinositol, also purified from bovine brain, restored catecholamine responsiveness. Solubilized preparations of myocardial adenylate cyclase bind 125-I-glucagon either in the presence of added phosphatidylserine, thereby providing a clear separation of the processes of activation and binding. Solubilized myocardial adenylate cyclase has a molecular weight of about 160,000. Sephadex G-100 chromatography of the solubilized enzyme following the binding of 125-I-glucagon to its myocardial receptor reveals two distinct peaks; one, having catalytic activity and a molecular weight greater than 100,000 and two, the binding material having no catalytic activity and a molecular weight of 24,000-28,000. These data are consistent with the presence of a dissociable glucagon receptor site. The role of this dissociation in the activation-inactivation of the enzyme remains to be explored. It is postulated that phospholipids induce the required configurational change in the catalytic site following the binding of hormone to its receptor, and by this means couples the receptor to the catalytic site. This model may be applicable to certain clinical situations. Cardiac adenylate cyclase is unresponsive to glucagon in chronic congestive heart failure. The defect may reside either in the binding of glucagon to its receptor site or in the metabolism of a specific acidic phospholipid such as phosphatidylserine.
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PMID:The glucagon receptor and adenylate cyclase. 16 52

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

The effects of isolated and combined use of strophanthin and glucagon on the values of central hemodynamics and cardiac contractile function were compared. The study was conducted on patients with myocardial infarction complicated by congestive heart failure in the acute period of the disease. It was found that a combination of these drugs had a synergic inotropic effect. A conclusion was drawn on the advantages of the combined use of strophanthin and glucagon in the treatment of severe congestive heart failure in the acute period of myocardial infarction.
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PMID:[Combined use of glucagon and strophanthin in myocardial infarct complicated by severe cardiac insufficiency]. 34 97

Apolipoprotein (apo) E is a predominant protein in developing mammalian brain and in damaged peripheral nerve. Of particular interest is the observation that astrocytes in the central nervous system cease to produce apoE after nerve damage, whereas an increase in apoE production results after peripheral nerve injury. Differences in the response to injury with regard to the production of apoE may be related to dissimilarities in the abilities of the central and peripheral nervous systems to regenerate. As there are few data concerning the regulation of apoE gene expression in extrahepatic tissues, we employed a human astrocytoma cell line (CCF-STTG1) as a model to study apoE production in astrocytes. CCF-STTG1 cells secreted apoE constitutively in serum-free media. Cholesterol added to the media as cholesterol:phospholipid liposomes (2-100 micrograms/ml) or as human plasma LDL increased the amount of apoE secreted into the media, but had little or no effect on the relative abundance of apoE mRNA. By contrast, the commercially available triglyceride-phospholipid emulsion Intralipid added at dilutions of 1:50 to 1:500 caused a total inhibition of apoE secretion by the cells, but again, little change was noted in the relative abundance of apoE mRNA. Insulin (5 micrograms/ml) caused a 45-55% reduction in the amount of apoE secreted by the astrocytoma cells. Glucagon (5 micrograms/ml), on the other hand, did not increase apoE secretion, and apoE mRNA concentrations were not affected by either hormone treatment. ApoE was secreted from the astrocytoma cells associated with particles of plasma VLDL to IDL and HDL size. After feeding the cells with 20 micrograms/ml cholesterol as cholesterol:phospholipid liposomes, an increased proportion of apoE was secreted associated with the larger VLDL to IDL size particles, with a concomitant decrease in the proportion associated with the smaller HDL-size particles. When cells were incubated with 5 micrograms/ml insulin, most of the apoE was associated with the HDL-size particles. When cholesterol:phospholipid liposomes were added in the presence of insulin virtually all of the secreted apoE was found associated with the VLDL to IDL size particles. In summary, the regulation of apoE production in CCF-STTG1 cells in many respects resembles that of other cells, including hepatocytes. However, it is clear that there remain to be identified cell specific factors which regulate apoE production in astrocytes. The CCF-STTG1 cell line promises to provide a suitable model to investigate these questions.
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PMID:Secretion of apolipoprotein E by an astrocytoma cell line. 140 94

Hypoglycemia is an underappreciated and potentially fatal complication of insulin and sulfonylurea treatment of diabetes mellitus in the elderly. After several years of diabetes, patients typically lose glucagon and epinephrine responses to hypoglycemia, resulting in loss of adrenergic warning symptoms, as well as prolongation of hypoglycemic episodes. Also of pertinence to the elderly, renal disease, liver disease, congestive heart failure, hypothyroidism, hypoadrenalism, medications, and inadequate monitoring may also contribute to hypoglycemia. The benefits of tight control can be observed only if it is applied to appropriately selected patients.
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PMID:Hypoglycemia: still a risk in the elderly. 240 23

In healthy subjects intravenous glucagon administration induces a prompt (at 1 h) fall in serum T3 concentration and a later (at 4 h) rise in biologically inactive rT3. Since high levels of plasma glucagon have frequently been found in some patients with severe chronic illnesses, together with an anomalous thyroid condition (low serum T3, high serum rT3), it has been supposed that hyperglucagonemia could play a pathogenetic role in causing selective T3 deficiency. In the present study fasting plasma glucagon concentration was measured in 48 patients with low T3 and severe nonthyroidal illnesses: hepatic cirrhosis in 16 cases, chronic non-A non-B hepatitis in 4 cases, uncontrolled type II diabetes mellitus in 5 cases, renal failure in 12 cases, congestive heart failure in 5 cases, tumor in 16 cases. In comparison with a group of 21 healthy controls fasting plasma glucagon concentration was significantly higher in the patients (198.75 +/- 13.20 pg/ml vs. 127 +/- 6.80 pg/ml; p less than 0.001). However, only 29 patients (60.4%) had elevated plasma glucagon levels, whereas 19 (39.5%) had abnormal plasma glucagon levels. Furthermore, no significant difference was found between the thyroid hormone pattern of the patients with hyperglucagonemia and of the patients with normal glucagonemia. On the other hand, a significant correlation between plasma glucagon concentrations and serum T3 and rT3 concentrations was not found. All these findings indicate that in patients with severe chronic illnesses the fall in circulating T3 cannot be due to hyperglucagonemia only which, therefore, might simply be a contributory factor together with other as yet unidentified disorders.
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PMID:[Role of high blood glucagon in the reduction of serum levels of triiodothyronine in severe non-thyroid diseases]. 263 98

Hypoglycemia associated with renal failure is more common than generally thought. Its occurrence is often a marker of multisystem failure and has an ominous prognostic implication. Its pathogenesis is frequently complex and involves one or several mechanisms. In the evaluation of uremic hypoglycemia, the first step should be the exclusion of obvious causes such as insulin, oral hypoglycemic agent therapy, and the use of drugs known to cause hypoglycemia. Propranolol, salicylates, and disopyramide are among the most commonly implicated agents. Additional triggering events are alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency. When no obvious cause can be demonstrated, the hypoglycemia is referred to as spontaneous. Spontaneous uremic hypoglycemia has been attributed to deficiency of precursors of gluconeogenesis, that is, alanine, deficient gluconeogenesis, impaired glycogenolysis, diminished renal gluconeogenesis and impaired renal insulin degradation and clearance, poor nutrition, and, in a few cases, deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon. However, the mechanism(s) seems to differ from one patient to the other. Dialysis also predisposes to hypoglycemia in uremia, possibly because of the chronic state of malnutrition. Postdialysis hypoglycemia is secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate. In uremic hypoglycemia, neuroglycopenic manifestations predominate because of frequent autonomic nervous system dysfunction and lack of catecholamine release in response to hypoglycemia. Its severity and duration are variable. Hypoglycemia should be suspected in any patient with renal failure who exhibits any change in mental or neurologic status. Detection of hypoglycemia should rely on frequent and careful glucose determinations in any patient with uremia.
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PMID:Hypoglycemia associated with renal failure. 264 22

Although early experiments in animals and humans suggested that digitalis glycosides increased cardiac output only in the failing heart, later studies showed that these cardiotonic agents increase intraventricular systolic pressure and decrease relaxation time in the normal animal. The controversy concerning the peripheral vascular or direct cardiac effects of digitalis was finally resolved when new methods were applied to the study of the effects of this drug on intraventricular pressures and cardiac contractile force. Other positive inotropic agents, such as the adrenergic agonists, have also been tested for the treatment of heart failure. However, during long-term oral or intravenous therapy, the effectiveness of these drugs appears to diminish. Clinical studies of glucagon, a polypeptide with positive inotropic and chronotropic effects, have revealed its potential for causing side effects and its reduced activity in patients with chronic heart failure. With the discovery of several new types of inotropic agents, i.e., the bipyridines and the imidazole and benzimidazole derivatives, interest in revising our therapeutic approach to congestive heart failure has increased. This review discusses recent developments in this area.
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PMID:Historical perspectives on inotropic agents. 351 Jul 79

The central and peripheral vascular haemodynamic effects of glucagon were studied in 29 patients. With a single dose method of 2 or 5 mg. glucagon intravenously the inotropic action of the drug produced immediate increased myocardial contractility with significant increase in cardiac output and enhanced cardiac performance, and lowering of pulmonary arterial pressure and pulmonary vascular resistance. No primary peripheral vascular effect was evident, and the increased systemic pressure and lowered systemic resistance appear to be secondary to the central action of the drug. With the dosage used there were no undesirable side-effects apart from a feeling of slight nausea. Though the haemodynamic effects are abrupt, reaching their maximum values in the first 10 minutes after injection, they tend to be dissipated within half an hour, presumably due to the very rapid destruction of the drug. Repeated booster doses rather than continuous infusion may be the method of choice to maintain an increased cardiac output. The positive chronotropic action of the drug may cause transient palpitations. Glucagon increased the cardiac output in the acute phase of myocardial infarction by 42 per cent. The haemodynamic effects in chronic rheumatic heart disease are more varied, and it may increase left atrial pressure in mitral stenosis, which is undesirable. Hyperglycaemia results from liver glycogenolysis but blood sugar levels rarely exceeded 200 mg./100 ml. These results warrant further study of the value of glucagon as a positive inotropic agent in low output heart failure, especially in acute myocardial infarction with cardiogenic shock, or after cardiac surgery, or in unrelieved chronic congestive heart failure.
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PMID:Haemodynamic effects of glucagon. 542 74

Most of the clinical problems experienced by the IDM in the immediate neonatal period are manifestations of abnormal fetal developmental physiology that occur in response to an increased flux of glucose from mother to fetus. The principal fetal responses are hyperglycemia, hyperinsulinemia, increased metabolic rate, and hypoxemia. Those fetal responses very likely lead to a redistribution of cardiac output, increased release of norepinephrine, and blunted release of glucagon. More fat is stored in adipocytes; more glycogen is stored in the liver; the heart may develop asymmetric septal hypertrophy; and lung metabolism is altered to delay the appearance of mature surfactant. At birth, the macrosomic IDM develops hypoglycemia that has a multifactorial basis (hyperinsulinemia, hypoglucagonemia, and probably diminished gluconeogenic and cortisol production rates). The IDM may experience respiratory symptoms from one of three causes: IRDS, persistent pulmonary hypertension, or congestive heart failure. Hyperbilirubinemia may occur because of increased rate of hemolysis; hypocalcemia and hypomagnesemia are likely within the first 3 days in association with a sluggish PTH response; and abnormal levels of inhibitors of fibrinolysis and platelet prostaglandin E-like substances may stimulate abnormal thrombosis.
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PMID:Infants of diabetic mothers. Fetal and neonatal pathophysiology. 638 22


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