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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 7 healthy-hearted probands the arterial-coronary-venous oxygen difference for glucose, K+, lactate, pO2, pCO2 and pH during a glucagon infusion was determined and compared with the values before and 10 minutes after infusion. Contradictory to the unchanged myocardial lactate extraction and the positively or negatively influenced K+-uptake recorded in the literature, in this contingent there was a statistically significant myocardial lactate production and an unchanged potassium uptake. The respiratory quotient of the heart increased. These changes are regarded as the result of a direct hormonal influence on the myocardial metabolism and have nothing to do with the change of an aerobic into an anaerobic metabolic state.
Basic Res Cardiol
PMID:[Myocardial metabolism under intravenous infusion of glucagon (author's transl)]. 23 1

The effect of glucagon on the circulatory system was studied in 22 healthy men. The drug was administered in doses of 50 microgram/kg of body weight for 30 sec. In the case of 5 subjects, arrhythmias occurred that manifested themselves as ventricular and supraventricular extrasystoles. In the case of 1 subject, who had sporadic ventricular fusion beats in the preexamination period, the arrhythmia increased following glucagon injection.
Eur J Cardiol 1978 Feb
PMID:Cardiac arrhythmias after intravenous administration of glucagon. 63 Nov 80

In the cases of 10 cardially healthy humans and 5 patients with heart disease, the left ventricular pressure as well as different parameters of contractility - deduced from the pressure curve and its first derivative - were determined by a catheter-tip manometer (Statham SF - 1). In particular the following values were concerned: dP/dtmax,-dP/dtmaxDP, the maximal calculated shortening velocity of the contractile elements according to the 2-component heart muscle model (VCEmaxTP) as well as with the Maxwell model (VCEmaxDP) and finally the (extrapolated) maximum shortening velocity (Vmax) under a fictive zero load. The examinations were carried out before and during a 10-minute infusion of 60 mg/kg glucagon and 10 minutes after completing the infusion. Besides glucagon also digoxin, etilefrin-HCl-1) and orciprenaline-2) were delivered and the same measurements were performed as with glucagon. A definite statement about the priority of any one of the named indices of contractility is rendered more difficult, because the enddiastolic pressure does not change substantially with glucagon. An unequivocal demarcation of frequency and pressure effects and of inotropic mechanisms as just as impossible, because, with the exception of VmaxDP, all parameters react quantitatively and qualitatively in an equal manner. On the basis of VmaxTP the result of glucagon is only a slight increase in the myocardial contractile capability, which would hardley suffice for the treatment of patients, who do not respond to digitalis. The decline of VmaxDP under glucagon cannot be explained. Under digitalis, etilefrin and orciprenaline, a similar dissociation of values for the maximum shortening velocity according to the 2- or 3-component-model of the heart muscle cannot be demonstrated.
Basic Res Cardiol
PMID:[The effect of intravenous infusion of glucagon on the contractility of the left ventricular myocardum in man (author's transl)]. 113 61

The hormonal regulation and enzymatic basis of endogenous lipolysis in heart are not yet completely elucidated. The lysosomal fraction from rat heart appeared to be markedly enriched in triglycerides and a significant reduction in triglycerides in this fraction was found after prolonged perfusion or stimulation of lipolysis with glucagon. The enhanced rate of lipolysis, measured as glycerol release from the isolated perfused rat heart, was abolished 10-15 min after continuous glucagon administration. Omission of glucagon for another 60 min restored the ability of glucagon to stimulate lipolysis, indicating the limited availability of endogenous triglycerides and the presence of a transfer-system for triglycerides from a non-metabolically active pool to a metabolically active pool. The enhanced lipolysis induced by low-flow ischemia was found to be inhibited by the lysosomotropic agent methylamine (5 mM). Methylamine-perfusion during low-flow ischemia was accompanied by an increased recovery of myocardial triglycerides in the lysosomal fraction. The possible role of lysosome-like particles in myocardial triglyceride homeostasis was further investigated by studying the kinetics of uptake and degradation of labeled triglycerides by membrane-particles recovered in the subcellular fraction enriched with lysosomal marker enzymes. It appeared that isolated lysosomal membranes take up added triglycerides at an average rate of 30 nmoles/min/g protein. The bulk of these triglycerides taken up is stored whereas 20% is degraded to diglycerides and free fatty acids. More than 90% of the free fatty acids formed were released from the lysosomes into the supernatant. The uptake and degradation of triglyceride-filled liposomes by isolated myocardial lysosomes was inhibited during incubation with methylamine (5 mM). On the other hand, a lowering of pH during in vitro incubation increased the rate of uptake and degradation of added triglycerides by isolated lysosomes. These results indicate that lysosomes or lysosome-like particles are involved in the enhanced lipolysis during myocardial ischemia.
Basic Res Cardiol
PMID:Involvement of lysosome-like particles in the metabolism of endogenous myocardial triglycerides during ischemia/reperfusion. Uptake and degradation of triglycerides by lysosomes isolated from rat heart. 235 Mar 29

Beta 2 adrenoceptors have been subdivided into beta 1 and beta 2 receptors, both by the varying response of different tissues to sympathomimetic amines and, more recently, by radioligand-binding techniques. It would appear that beta 1 receptors occur predominantly in the heart, whereas beta 2 receptors are found in lungs, peripheral blood vessels and uterus, and are also involved with glycogenolysis and glucagon and insulin secretion. In addition, the distribution of beta 1 receptors appears to relate to the density of sympathetic innervation of an organ or tissue, but tissues without sympathetic innervation are found to contain beta 2 receptors. Thus, beta 1 adrenoceptors may be considered as physiologically innervated receptors mediating responses to neuronally released norepinephrine, and beta 2 receptors as mediating responses to circulating catecholamines, particularly epinephrine. Radioligand-binding studies have also shown that the heart contains beta 2 receptors and the lung beta 1 receptors, but these are in the minority, and their role has not been identified. For many years, cardioselective beta 1-adrenoceptor antagonists have been available. This was considered to be a dose-dependent phenomenon but recent evidence has cast doubt on the concept that cardioselectivity is lost during dose increases within the therapeutic range. Nevertheless, even small doses of cardioselective drugs may show some beta 2-receptor antagonism, and may have adverse effects on patients with obstructive airways disease. Finally, nonselective drugs may result in a diastolic pressor effect in the presence of circulating catecholamines in contrast to the "vascular sparing" seen with cardioselective drugs.
Am J Cardiol 1987 May 15
PMID:Pharmacologic aspects of cardioselectivity in a beta-blocking drug. 288 70

Inotropic responses to isoproterenol of hypertrophied hearts have been shown to be decreased. We have previously reported that in 13-week-old spontaneously hypertensive rats (SHR) this decrease is probably due to decreased beta-adrenergic receptor number, while in hearts from two kidney-one clip renal hypertensive rats (2K-1C RHR), this is due to a decreased nucleotide regulatory protein activity. We now show that changes in 2K-1C RHR are time dependent. One week after instituting development of hypertension the heart is already hypertrophied. Biochemical changes consistent with decreased glucagon receptors are seen, as well as beginning changes consistent with decreases in the nucleotide regulatory protein activity. By two weeks this is more evident. Hypertrophy and biochemical changes can be reversed up to six weeks, but by ten weeks the activity of the catalytic subunit of the adenylate cyclase system is decreased. In 1K-1C RHR, biochemical changes in the cyclase system are accelerated as compared with the 2K-1C model. In SHR, changes in 24-week-old rats are the same as in the 13-week-old rats. It is concluded that in cardiac hypertrophy associated with different models of hypertension the decreased inotropic responsiveness to isoproterenol is associated with different biochemical defects in the beta-adrenergic receptor response coupling pathway, and that reversal in function occurs only when there is no apparent change in the catalytic subunit of the adenylate cyclase complex.
J Mol Cell Cardiol 1985 Jun
PMID:Adenylate cyclase activity during development and reversal of cardiac hypertrophy. 316 Aug 64

The inotropic responses of chronic alcoholic and control rat hearts to phenylephrine, glucagon, ouabain, and dobutamine were studied to determine if the reported beta-adrenergic subsensitivity of alcoholic rat hearts was a specific defect. Male Long-Evans rats were maintained on nutritionally-complete liquid diets for 10 to 12 months; alcoholic rats received 38% of their calories from ethanol. Dry heart weight/body weight ratios indicated an average 15% hypertrophy of the alcoholic rat hearts. The function of isolated working hearts from these animals was studied at a constant heart rate and afterload. Ventricular function curves indicated significantly lower basal function of alcoholic rat hearts, as evident from their lower peak left ventricular relaxation rate, lower isovolumic relaxation rate, and lower peak power compared to controls. The alcoholic rat hearts had significantly lower inotropic (stroke work and peak power) responses to phenylephrine, glucagon, and dobutamine compared to controls, whereas the response of the alcoholics to ouabain was not significantly different from that of controls. Oxygen supply-to-utilization ratios decreased similarly in alcoholics and controls during treatment with the inotropic agents, as a result of increases in myocardial oxygen consumption and effects on coronary flow that were similar in both groups of animals. Thus the differences in inotropic responses observed with the alcoholic rat hearts were not primarily the result of compromised oxygen supply. Rather, the decreased stroke work response of the alcoholic hearts which occurred despite an increase in oxygen consumption suggested that the alcoholic rat hearts did not utilize oxygen as efficiently as did control hearts to perform external work. This was reflected in the significant differences between alcoholics and controls in the response of calculated external work efficiency to phenylephrine, glucagon, and dobutamine. Thus, alcohol-induced cardiac hypertrophy was associated with depressed basal left ventricular contractile function and decreased responsiveness to alpha 1-adrenergic, beta 1-adrenergic, and glucagon stimulation, but the responsiveness to ouabain was not significantly affected. These characteristics are similar to those of hearts hypertrophied by other causes.
J Mol Cell Cardiol 1987 Nov
PMID:Alcoholic cardiomyopathy in rats: inotropic responses to phenylephrine, glucagon, ouabain, and dobutamine. 343 59

Controversy exists in the literature concerning the effects of insulin and glucagon on cardiac muscle contractility, in particular during anoxia, ischemia or sepsis. The purpose of the present study was to determine the effects of insulin and glucagon on the systolic function of the normal and the dysfunctioning septic rat myocardium in the Langendorff preparation. In the normal isolated rat heart, neither insulin nor glucagon exhibited any lasting inotropic effect on systolic function or coronary flow. Sepsis (cecal ligation and puncture) resulted in a dramatic reduction of systolic function to 44% of control animals. All insulin-containing formulations tested improved systolic function in septic hearts by a mean of 85% compared to Krebs and glucose only. However, this improvement did not reach statistical significance compared to the use of Krebs and glucose only. Glucagon at 100 micrograms/l was doing as well as Krebs and glucose alone while at 1 mg/l glucagon was only able to maintain pre-perfusion contractility. Our results suggest that neither insulin nor glucagon seem to possess special inotropic properties for the isolated perfused normal or septic rat heart.
Basic Res Cardiol
PMID:The effect of insulin and glucagon on systolic properties of the normal and septic isolated rat heart. 390 99

Ligation of the anterior descending coronary artery two-thirds from its origin in the pig was found to precipitate ventricular arrhythmias and fibrillation, starting approximately 20 min post-ligation, which were associated with regional accumulation of myocardial cAMP in the ischaemic area. When the arrhythmias stopped, cyclic AMP levels in the ischaemic zone were decreased. Arrhythmias could then be induced by subepicardial infusion (10 microliter/min) close to the visible edge of ischaemia of cAMP analogues [N6-monobutyryl cAMP, N6,O2'-dibutyryl cAMP (5.10(-2) M each)] or agents which increase the myocardial contents of cAMP. These agents were: isoproterenol (10(-6) M), noradrenaline, adrenaline (10(-5) M each), glucagon, histamine (10(-3) M each), theophylline and caffeine (5.10(-2) M each). Also active were dopamine (10(-3) M), ouabain (10(-5) M) and aconitine (10(-6) M). The arrhythmias induced by infusion of catecholamines were dependent on Ca2+ and were abolished by beta-adrenoceptor blocking agents (pindolol, 10(-6) M) and calcium antagonists (isoptin, D 600, 10(-4) M each). Infusion of 150 mM sodium chloride or 100 mM sodium butyrate did not precipitate arrhythmias. It is concluded that myocardial cAMP may play an important role in the genesis of ventricular arrhythmias in the ischaemic heart, probably by augmenting the slow calcium inward current.
Basic Res Cardiol
PMID:Cyclic AMP mediated arrhythmias induced in the ischaemic pig heart. 611 88

Although rare, acute poisoning with beta-blockers can be serious. Including the four personal cases of the authors, 40 cases of propranolol overdose have been published, with 8 deaths. Hypoglycaemia was not reported, but the association with alcohol can be very serious. One case of bronchospasm and one case of acute pulmonary oedema have been reported. Bradycardia is not the rule and widening of the QRS complex was reported in 4 cases. The other cases published are: 1) 10 cases with oxprenolol (including 5 cases of coma and 4 deaths), 2) 9 cases with acebutolol (2 deaths) including 5 with studies of the kinetics of the product (1 personal case), 3) 7 cases with pindolol (no bradycardia, good prognosis), 4) 6 cases (1 personal) with metoprolol (4 cases of massive ingestion with 1 death), 5) 3 cases with alprenolol (1 death), 6) 4 cases with sotalol (2 cases of turned apex, 1 death), 7) 1 case with atenolol. The authors discuss the practical management. They stress that glucagon is a much better form of treatment in severe cases than isopropylnoradrenaline, and that the crucial period is in the first few hours after the ingestion of the beta-blockers, i.e. usually before the patient's arrival at the hospital. The effectiveness of endocavity stimulation has not been demonstrated.
Ann Cardiol Angeiol (Paris) 1983 Jun
PMID:[Acute poisoning caused by beta blockers in the adult. Apropos of 7 cases]. 613 80


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