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)

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.
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PMID:Alcoholic cardiomyopathy in rats: inotropic responses to phenylephrine, glucagon, ouabain, and dobutamine. 343 59

1,3-Butanediol is an ethanol dimer that induces systemic ketosis. It has previously been shown to increase hypoxic survival time and reduce neurologic deficit in several experimental preparations. The aim of this study was to determine if the mechanism of 1,3-butanediol-induced cerebral protection was elevation of blood ketone levels, blood glucagon levels, or both. Blood beta-hydroxybutyrate levels, glucagon levels, or both produced by a previously reported protective dose of 1,3-butanediol (47 mmol/kg) were simulated by direct i.v. infusion of the ketone beta-hydroxybutyrate and glucagon separately and in combination, and the effect on hypoxic survival time in instrumented Levine rats (unilateral carotid ligation and hypoxic exposure) was determined. To test if the mechanism was a direct or osmotic effect of the alcohol, an equimolar dose of ethanol (47 mmol/kg) was administered and the effect on hypoxic survival time was compared with that produced by 1,3-butanediol. As in previous studies, 1,3-butanediol significantly increased hypoxic survival time (241% of control, Scheffe p less than 0.05). Various doses of beta-hydroxybutyrate and glucagon were infused to approximate the blood levels of beta-hydroxybutyrate and glucagon produced by a protective dose of 1,3-butanediol. Although beta-hydroxybutyrate or glucagon infusions produced blood levels of these substances that were comparable with those produced by administering butanediol, they failed to prolong hypoxic survival time as long as 1,3-butanediol. No correlation was detected between hypoxic survival time and blood levels of beta-hydroxybutyrate, glucagon, insulin, or glucose. An equimolar dose of ethanol did not significantly increase hypoxic survival time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated blood ketone and glucagon levels cannot account for 1,3-butanediol induced cerebral protection in the Levine rat. 381 Jul 56

Haemodynamic effects of pharmacological doses of insulin during acute ischaemic heart failure were studied in 8 dogs. Severe depression of left ventricular function was induced by the injection of 50 micron plastic microspheres into the left main coronary artery. This was demonstrated by a significant increase in left ventricular end-diastolic pressure and a significant decrease in the maximum rate of left ventricular pressure rise (LVdP/dtmax), stroke volume and cardiac output. Eighty-five minutes after the embolization procedure, 300 IU of insulin free of glucagon and calcium was injected as a bolus. This was followed by infusion of glucose and potassium to maintain physiological levels of these factors. Five minutes after insulin administration, there was a significant improvement in left ventricular performance as shown by decreased left ventricular end-diastolic pressure (P less than 0.01) and increased LVdP/dtmax (P less than 0.01), stroke volume (P less than 0.05) and cardiac output (P less than 0.05). A significant reduction in heart rate occurred. A non-significant increase in mean aortic blood pressure and reduction in total peripheral resistance were seen. In conclusion, pharmacological doses of insulin significantly improve cardiac pump function during acute ischaemic left ventricular failure in dogs.
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PMID:Haemodynamic effects of high doses of insulin during acute left ventricular failure in dogs. 389 50

Glucagon has been shown previously to increase further the enhanced tolerance for hypoxia observed in mice with elevated blood ketones. Glucagon is also known to increase blood glucose and to alter directly the metabolism of some (liver) cells. Both the increase in blood glucose and altered cellular metabolism could contribute to the increase in tolerance for hypoxia observed in mice given glucagon in combination with the ketone, beta-hydroxybutyrate. To evaluate the systemic component of this hypothesis, blood glucose, beta-hydroxybutyrate, and glucagon were elevated alone or simultaneously and hypoxic tolerance of mice was measured. To identify possible cellular effects of glucagon on glucose or ketone metabolism, we measured the incorporation of radiolabeled glucose or beta-hydroxybutyrate into CO2 or total lipid in isolated rat brain slices. Both glucagon and glucose increased hypoxic tolerance of ketotic mice but our data do not support the hypothesis that glucagon's action was only through an elevation of blood glucose. In brain slices glucagon stimulated the incorporation of beta-hydroxybutyrate into CO2 both in the presence or absence of additional glucose. These results demonstrate that glucagon has a direct effect on brain metabolism which may contribute to the increased tolerance for hypoxia. They, however, do not exclude the possibility that glucagon is working in addition to increase hypoxic survival in ketotic mice by increasing the availability of glucose to the brain.
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PMID:Glucagon stimulates ketone utilization by rat brain slices. 642 89

A coorelation has been observed between increased blood ketones and the tolerance of mice to hypoxia (4-5% oxygen). In previous studies fasted mice, alloxan diabetic mice and mice given 1,3-butanediol were found to be ketotic and to have increased tolerance to hypoxia. We attempted to induce a similar increased hypoxic tolerance by direct elevation of blood ketones with IV and IP beta-hydroxybutyrate (BHB). No increase in hypoxic tolerance was observed with BHB alone. Inasmuch as fasting and alloxan diabetes are both associated with elevated blood glucagon (G), hypoxic tolerance tests were made 30 min after G alone or a combination of G plus BHB. The mice given G alone or BHB alone had hypoxic survival times not different from saline controls. The mice given G plus BHB had increased survival times that could not be explained on the basis of a G mediated alteration in blood BHB.
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PMID:Hypoxic tolerance enhanced by beta-hydroxybutyrate-glucagon in the mouse. 677 95

The hemodynamic, hormonal and electrolyte effects of prenalterol, a synthetic selective beta 1 agonist, were studied in six patients with New York Heart Association functional class II and III heart failure. Prenalterol was infused incrementally at 60, 120 and 240 nmol/min, each rate for 24 hours, producing steady-state plasma prenalterol levels of 52 +/- 3, 121 +/- 6 and 194 +/- 9 nmol/1, respectively (mean +/- SEM). Hemodynamic and hormonal measurements were performed before, during and after prenalterol administration under conditions of constant body posture and a regulated intake of dietary sodium and potassium. Prenalterol induced a statistically significant increase in cardiac index (from 2.6 +/- 0.2 to 3.1 +/- 0.3 1/min/m2), with parallel increases in stroke index (from 28 +/- 2 to 34 +/- 2 ml/beat/m2). Forearm blood flow measurements increased (from 2.9 +/- 0.5 to 4.1 +/- 0.6 ml/min/100 g), while calculated systemic vascular resistance fell, as did pulmonary capillary wedge pressure (from 13.7 +/- 1.6 to 10.5 +/- 1.7 mm Hg). The drug did not alter heart rate, arterial pressure, right heart pressures or the frequency of ventricular premature beats. Prenalterol increased plasma renin activity (from 2.9 +/- 0.8 to 6.6 +/- 1.8 nmol/1/hour), angiotensin II (from 59 +/- 12 to 89 +/- 22 pmol/1), urinary aldosterone excretion (from 41 +/- 10 to 78 +/- 34 nmol/day) and plasma insulin (from 10.6 +/- 2.2 to 19.8 +/- 3.9 mU/1). Circulating catecholamines, cortisol, glucose, glucagon or pancreatic polypeptide did not change. Dose-response studies in five patients showed dose-dependent increments in hemodynamic variables, while hormonal changes plateaued at the second dose level. We conclude that prenalterol infusion augments myocardial contractility, reduces systemic vascular resistance, and stimulates insulin release and the renin-angiotensin-aldosterone system.
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PMID:Hemodynamic, hormonal and electrolyte responses to prenalterol infusion in heart failure. 682 3

The hemodynamic effects of intravenous labetalol (a combined alpha- and beta-blocking agent) were studied in 11 patients during early post-open heart surgery hypertension. With a mean dosage of 15 mg, labetalol reduced both systemic arterial pressures and the heart rate by an average of 21 percent (p < .001). The patients failed to compensate for the decline in pressure and pulse rate by elevation of their stroke volume, and even the cardiac index (CI) was severely depressed (from 2.30 to 1.67 L/min/m2, ie, 27 percent; p < .001). Neither left ventricular filling pressure nor vascular resistance was affected by labetalol early after open heart surgery. In four patients, 3 mg of glucagon after administration of labetalol elevated pulmonary arterial pressures and increased the CI by 16 percent. Two patients were observed on the preoperative day, and their response to labetalol was similar to that described in earlier studies: during blood pressure decline, CI was slightly augmented, and the systemic vascular resistance was greatly reduced (26 percent). The results indicate that after open heart surgery, patients are highly sensitive to the beta-blocking effects of labetalol, and although labetalol can greatly reduce myocardial oxygen consumption, it cannot be recommended for the treatment of post-open heart surgery hypertension.
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PMID:Combined alpha- and beta-blockade with labetalol in post-open heart surgery hypertension. Reversal of hemodynamic deterioration with glucagon. 700 97

In order to clarify insulinotropic effects of the myelin basic protein (MBP) we studied mode of association and distribution of MBP in the pancreatic islets and tested the insulin-releasing activity of various MBP peptides. Rat pancreatic islets were first stimulated in a static incubation with 10 microM bovine MBP (bMBP) at a substimulatory (3.5 mM) glucose concentration. The islets exposed to MBP released significantly more insulin and glucagon in a second incubation in the absence of added stimulant and in the presence of 11.5 mM arginine than the incubated, non-stimulated islets and islets initially stimulated with 15 mM glucose. Response to stimulation with 15 mM glucose in the second incubation by islets exposed first to MBP was impaired compared to incubated, non-stimulated islets. Immunoelectron microscopy showed that MBP had entered into the islet cells and associated with membranes of intracellular vacuoles, most of which represented enlarged, often fused insulin granules. MBP was also present at the islet edge and in the intercellular spaces. Of the purified MBP peptides of sizes of 4.8-13.6 kDa, produced from the digestion with brain acid proteinase and with pepsin and covering the entire bMBP sequence, only the large peptides (1-88, 9.8 kDa and 43-169, 13.6 kDa) stimulated insulin secretion significantly. Heterogeneous peptide mixtures, obtained from a time-course digestion of bMBP by myelin calcium-activated neutral protease, consisting of peptides of approximate molecular weights of 8-11 kDa and larger, also stimulated insulin release. The glucagon-releasing activity of MBP peptides was low and followed the same pattern as the insulin-releasing activity. The present results suggest that MBP-induced fusion of the membranes of hormone granules is involved in MBP-induced insulin release. The hormone-releasing activity of the large peptides in addition to that of the intact molecule is explained as being due to the ability of these peptides to associate with membranes. MBP-induced hormone release and related effects could be associated with neuropathological conditions such as stroke and multiple sclerosis.
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PMID:Evidence supporting membrane fusion as the mechanism of myelin basic protein-induced insulin release from rat pancreatic islets. 749 48

The central nervous system myelin basic protein (MBP) stimulates the release of several peptide hormones including insulin and glucagon. This could be associated with the development of hyperglycaemia in neurological disorders such as stroke, in which MBP is known to leak into blood circulation. In the present study the mechanism of insulin and glucagon release was investigated by using short-term incubation of isolated rat pancreatic islets. Incubation with MBP in the absence of Ca2+ resulted in approx. 11-fold stimulation of insulin and glucagon release. The stimulation dwindled with increasing Ca2+ concentration and was 6.5-fold at 0.5 mM and 2-fold at 2.5 mM Ca2+. When MBP and glucose at various concentrations were simultaneously present in the incubation mixture, stimulation of insulin release was the sum of the stimulation induced by these two agents separately both at the 0.5 and 2.5 mM Ca2+ concentrations. Glucose at concentrations of 10 or 15 mM did not suppress MBP-stimulated glucagon release. Caffeine-evoked increase in intracellular Ca2+ was without effect on MBP-stimulated insulin or glucagon release but enhanced glucose-induced insulin release. The Ca2+ channel blocker diltiazem had no effect on MBP-stimulated insulin release at concentrations where glucose-stimulated release was inhibited. Ruthenium red inhibited both MBP- and glucose-stimulated insulin release as well as MBP-induced glucagon release. Staurosporine (inhibitor of protein kinase C) had no effect on MBP-induced insulin release, although it partially inhibited glucose-stimulated release. Maleylation of MBP abolished its insulin- and glucagon-releasing activity by approx. 90%. These results suggest that MBP exerts its insulin-releasing effect by mechanisms different from those of glucose-stimulated insulin release and does not require Ca2+ channels or protein kinase C. The relation of MBP-induced insulin and glucagon release to Ca2+ concentration is probably explained by enhanced self-aggregation of MBP or by increased ability of MBP to interact with islet cell membranes in the absence of Ca2+, or both. It is concluded that MBP-induced hormone release appears to be mediated by membrane fusion and oligomerization of MBP. The mechanism thus resembles that of various toxins and other cytotoxic agents.
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PMID:Mechanism of the myelin basic protein-induced insulin and glucagon release from isolated rat pancreatic islets. 754 15

In a previous study of propranolol poisoning, glucagon and milrinone significantly increased cardiac output, but the improvement caused by glucagon was almost entirely due to the chronotropic effect. This study investigates the combined effect of glucagon, in a dose not inducing tachycardia, and milrinone on beta-blocker poisoning. Following the administration of 10 mg/kg propranolol IV over ten minutes, dogs (N = 20) were divided into four treatment groups, group S (saline), group G (glucagon 2.5 micrograms/kg), group M (milrinone 100 micrograms/kg), and group G + M (glucagon 2.5 micrograms/kg plus milrinone 100 micrograms/kg). Hemodynamic parameters were observed over the next thirty minutes. Heart rate, cardiac output, and mean arterial pressure were decreased in all groups after the administration of propranolol. Heart rate, mean arterial pressure, cardiac output, and stroke volume recovered to the baseline values in group G + M. However, heart rate in group G + M showed a significant increase versus the other three groups. In a canine model of severe propranolol poisoning, the combined effect of glucagon 2.5 micrograms/kg and milrinone 100 micrograms/kg brought about a significant hemodynamic improvement, but it was accompanied by an excessive increase of heart rate. Combined therapy of milrinone and glucagon may not be preferable therapy in beta-blocker poisoning in the canine model.
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PMID:Combined use of glucagon and milrinone may not be preferable for severe propranolol poisoning in the canine model. 762


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