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)

In an isolated rat liver perfusion system the effects of normothermal ischemia on hepatic functions were investigated. After 30 minutes of anoxy bile production and BSP elimination capacity of the liver are significantly reduced. The quantity of secreted "ascites" from the surface of the liver several times high after anoxic damage, while oxygen consumption, portal venous pressure and ammonia elimination do not differ significantly from the controls. Pretreatment with insulin plus glucose, isoproterenol, hypoxanthine, chlorpromazine and glucagon (5 micrograms/100 g i.v., or 0.2 mg/100 g s.c.) does not reduce noticeably the normothermal anoxic lesion of the liver Glucagon (50 micrograms/100 g i.v.), allopurinol, dibenzyline, ATP-MgCl2 and aspartic acid enhance significantly the ischemia-tolerance of liver in vitro.
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PMID:Ischemic damage of the liver. Part I: In vitro investigation of the prevention of the ischemic lesion of the liver. 49 24

A new model for the study of ischemic liver lesion on rats has been worked out. Pretreatment with allopurinol, dibenzyline, methylprednisolone, glucagon, ATP-MgCl2 and aspartic acid reduced the overall mortality of ischemic liver injury. Administered after the anoxic hepatic lesion only glucagon and aspartic acid had beneficial effect on the survival rate. Under the influence of 30 minutes of normothermal ischemia the DNA synthetizing ability of the liver decreased. Aspartic acid, glucagon and ATP-MgCl2 significantly enhanced the regeneration of the ischemically damaged liver. These procedures might be suitable for donor pretreatment in liver transplantation, as well as for the treatment of other pathological states, causing a normothermal ischemia of the liver.
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PMID:Ischemic damage of the liver. Part II: In vivo investigation of the prevention of the ischemic lesion of the liver. 49 25

We compared the effectiveness of three pharmacologically and chemically dissimilar vasodilators (histamine, glucagon, and perhexiline) in reversing the hemodynamic and metabolic deficits of intestinal ischemia produced by hemorrhage. With intraarterial infusion into the superior mesenteric artery of anesthetized control dogs, all three agents increased mesenteric blood flow and oxygen consumption without altering systemic arterial blood pressure. Similarly, in the ischemic gut following moderate hemorrhage all three vasodilators increased mesenteric flow and oxygen consumption while reducing vascular resistance and not affecting systemic arterial blood pressure. On a molar basis glucagon was the most potent dilator drug. In severely hemorrhaged dogs whose intestinal blood flow had been reduced nearly 80%, glucagon restored oxygen uptake and vascular resistance to control levels. These findings demonstrate the efficacy of three different vasodilators in reversing the mesenteric ischemia and hypoxia produced by hemorrhage.
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PMID:Effects of vasodilators on mesenteric ischemia and hypoxia induced by hemorrhage. 49 29

Eleven adult mongrel dogs were divided into two groups. Group 1 animals served as controls and Group 2 received propranolol (6 mg/kg/day) orally in divided doses for 15 to 21 days. Prior to cardiopulmonary bypass, cardiac output, first derivative of left ventricular pressure (dp/dt), peak systolic pressure, heart rate, and central venous pressure were recorded. The animals were then placed on cardiopulmonary bypass and subjected to 30 minutes of global ischemia at the myocardial temperature of 32 degrees C. Following cessation of cardiopulmonary bypass the baseline studies were repeated. In Group 2 animals following the repeat studies, glucagon was administered at a rate of 0.13 microgram/kg/min. The cardiac index and dp/dt were decreased by 43.3% (p less than 0.001) and 40.5% (p less than 0.001) in comparison to Group 1 animals. In Group 2 dogs, after bypass and glucagon infusion, cardiac index increased by 38% (p less than 0.02), dp/dt rose by 78% (p less than 0.05), and peak systolic pressure increased by 24.8% (p less than 0.05). These studies show the benefit of glucagon in the treatment of low cardiac output in the presence of beta-adrenergic blockade.
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PMID:The effect of glucagon in animals on chronic propranolol therapy. 63 10

Previous studies have been shown that intravenous cardiac glycosides produce mesenteric vasoconstriction (MVC). The possibility that this might critically compromise blood flow in patients with mesenteric vascular disease was suggested. To evaluate whether MVC occurs with intravenous cardiac glycosides in the presence of proximal mesenteric artery stenosis, blood flow in the superior mesenteric artery (SMA) of thirteen dogs was measured with a Doppler flowmeter. The SMA was constricted and pressures were measured in the aorta, SMA, and superior mesenteric vein. Superior mesenteric vascular resistance (SMVR) was calculated by dividing the pressure difference between the SMA and superior mesenteric vein by the total blood flow to the superior mesenteric vasculature and was reported as mm Hg/cc-min. Blood flow was measured simultaneously by a drop rate meter in the vein of a surgically isolated intestinal segment supplied by a single arterial arcade. Venous outflow pressure from this segment was also monitored, which allowed calculation of isolated gut segment resistance (IGSR) in mm Hg/cc-min per 100 g gut. Stenosis of the SMA produced pressure gradients of 10 to 75 mm Hg and decreased resting blood flow by as much as 82%. Digoxin produced an increase in both SMVR and IGSR throughout the 30 to 120 minute period of the study in thirteen dogs despite the presence of severe grades of SMA stenosis. There was no relationship between the degree of proximal SMA stenosis and the magnitude of resistance change due to digoxin. To determine if this MVC was reversible, glucagon was administered to eleven dogs 30 to 60 minutes after digoxin and completely overcame the constriction. Thus, digoxin produced MVC in the presence of proximal SMA stenosis. This MVC was pharmacologically reversible. These data suggest that intravenous digoxin might contribute to intestinal ischemia in patients with preexisting vascular disease.
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PMID:Digoxin induced intestinal vasoconstriction. The effects of proximal arterial stenosis and glucagon administration. 80 76

Glucagon in small intravenous (i.v.) doses markedly increases glomerular filtration rate (GFR) in normal anesthetized dogs. In this study, the effects of glucagon 5 mug/min (i.v.) on renal hemodynamics was tested in four canine models of acute pre-renal failure (hemorrhage, barbiturate overdose; renal arterial clamping and renal arterial infusions of noradrenaline) and in a model of unilateral acute tubular necrosis at 4 h and 6-7 days following completion of the ischemic insult. Following hemorrhage and barbiturate excess, with arterial blood pressure maintained at 65-70 mm Hg, whole-kidney GFR and clearance rate of p-aminohippurate decreased by 50-70%. During this reduction of perfusion pressure, the subsequent infusion of glucagon increased GFR by 90-130%. In models where arterial pressure was normal during the period of ischemia (clamping and noradrenaline infusion), not only did glucagon significantly increase renal perfusion, but the ischemic kidney proved to be far more sensitive to the hemodynamic effects of glucagon (delta GFR - 120-160%) than the contralateral control (deltaGFR = 30-40%). In three dogs completely anuric following renal arterial clamping, glucagon was able to improve blood flow and restart urine formation. Glucagon, but not dopamine, was able to simulate the beneficial effects of hypertonic mannitol on renal function in dogs with hemorrhagic hypotension. Glucagon was without effect in established acute tubular necrosis. This study, therefore, indicates that, during renal ischemia, glucagon may be quite effective in preserving urine output and perfusion of the kidneys.
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PMID:The effect of glucagon on glomerular filtration rate in dogs during reduction of renal blood flow. 117 90

Metabolic disturbances in the canine liver during warm ischemia by Pringle's method for 60 minutes and the role of Coenzyme Q10 (CoQ10), Prostaglandin E1 (PGE1) and ONO-3708, TXA2 receptor antagonist, were studied. Mongrel dogs were divided into five groups; control group, group of liver ischemia without drugs, groups of liver ischemia with CoQ10, PGE1 and ONO-3708 pretreatment. Metabolic rates of PGI2, TXA2, insulin, glucagon and glucose and production of lipid peroxides in the five groups were measured at the points before Pringle's procedure, 5 minutes, 60 minutes and 120 minutes after declamping. In the group of ischemia without drug administration, the hepatic metabolism of PGI2, TXA2, insulin and glucose were decreased after declamping. The metabolism of glucagon, however, was not disturbed by warm ischemia. The production of lipid peroxides increased at 5 minutes after declamping. In the groups of CoQ10, PGE1 and ONO-3708 pretreatment, changes of PGI2, TXA2 and insulin metabolism in the liver were improved, and an increased production of lipid peroxides by warm ischemia was normalized. This study suggests that CoQ10, PGE1 and ONO-3708 protect liver damage by warm ischemia as results of improvement of metabolic disturbances of PGI2, TXA2, insulin and suppression of lipid peroxides production.
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PMID:[Assessment for protective effects of CoQ10, PGE1 and TXA2 receptor antagonist (ONO-3708) on warm ischemic liver]. 138 60

Adult white rabbits were subjected to 2 hours of partial cardiopulmonary bypass (flow rate 90 ml/min/kg) at 32 degrees C, and unilateral pulmonary artery occlusion was used to simulate total cardiopulmonary bypass in the lung subjected to arterial occlusion, with the other side used as the control lung. The lung subjected to arterial occlusion was reperfused by one of the following methods: (1) by whole blood (WB group), (2) by leukocyte-depleted blood (LD group), and (3) by whole blood with protease inhibitor (nafamostat mesilate, FUT group), expecting its anticomplement action. In the fourth group, the lung was inflated with oxygen during pulmonary artery occlusion followed by whole blood reperfusion (OXY group). As a result, lungs subjected to pulmonary artery occlusion showed significant decreases in tissue concentrations of adenosine triphosphate and regional tissue blood flow during cardiopulmonary bypass. Furthermore, recovery of adenosine triphosphate was depressed in the WB group and recovery of regional tissue blood flow in the WB and OXY groups. Ultrastructural findings in alveolar epithelial cells and capillary endothelial cells showed worsening at reperfusion in only the WB group. Transpulmonary gradients of C5a and leukocyte showed significant increases at reperfusion in the WB and OXY groups. Alveolar-arterial oxygen difference was significantly higher in the WB group than in the others. Results indicate that complete cessation of pulmonary artery flow in normothermic cardiopulmonary bypass may cause ischemia of the lung followed by reperfusion injuries with the no-reflow phenomenon, with possible involvement of activation of leukocytes and complement.
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PMID:Experimental study in a rabbit model of ischemia-reperfusion lung injury during cardiopulmonary bypass. 154 56

Seizures are a documented complication to cerebral ischemia. After 10 min of forebrain ischemia in rats, preischemic hyperglycemia invariably leads to severe, most often fatal epileptic attacks. This outcome is related to the exaggerated lactic acidosis, which has been suggested as a possible contributor to severe membrane changes and widespread edema. To find out if circulating hormones or plasma energy substrates modulate this additive damage caused by the hyperglycemia, plasma concentrations of of corticosterone, epinephrine, norepinephrine, dopamine, glucagon, insulin, glucose, free fatty acids (FFA), 3-hydroxybutyrate, and acetoacetate were measured before and in the early recirculation period after 15 min of forebrain ischemia in the rat. Plasma corticosterone levels did not differ between the normo- and hyperglycemic groups. Although not significantly different from control, the catecholamine levels showed a tendency to be higher in the hyperglycemic groups. Therefore, because catecholamines have been reported to have a protective effect during ischemia the present result cannot explain why hyperglycemia aggravates the ischemic damage. Insulin levels seemed to increase during ischemia but not significantly. Levels quickly returned to normal after 30 min of recirculation. FFA concentrations were reduced after the induction of ischemia and appeared lower in all hyperglycemic groups. The level of one of the ketone bodies, 3-hydroxybutyrate, showed a significant decrease in hyperglycemic ischemia in all groups compared with normoglycemic ischemia. The same tendency was seen for acetoacetate. Results are compatible with a protective role of ketone bodies in ischemia. It is concluded that among the hormones and substrates studied only the ketone body concentrations qualify as a modulator of the exaggerated brain damage after ischemia in hyperglycemic subjects.
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PMID:Ischemia in normoglycemic and hyperglycemic rats: plasma energy substrates and hormones. 211 Apr 23

Controversy still exists in the published literature about the need for administration of intravenous glucose during liver transplantation. The ability of the grafted liver to metabolize insulin and glucagon and the appropriateness of secretion of these hormones are addressed in the present study. Two groups of pigs received unstored liver autografts, one with free infusion of 10% glucose and the other with limited infusion of 2.5% glucose solution, while attempting to maintain plasma glucose levels less than 200 mg/100 ml. In these animals, irrespective of moderate or major hyperglycemia, serum insulin levels were appropriate for blood glucose concentrations. However, in both groups, plasma glucagon levels rose three- to fourfold more than preoperative values and were inappropriate. Although facilities for measurement of blood flow were not available, application of the technique of transhepatic sampling has revealed that hepatic handling of insulin seems to be unimpaired after autograft with limited ischemia. Pancreatic secretion of glucagon, however, appeared to increase during the period immediately after revascularization. It is suggested that transhepatic sampling methods may be used in experimental transplantation to elucidate the effects of storage for prolonged periods.
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PMID:Transhepatic sampling during experimental porcine liver autotransplantation--its application to measurements of insulin, glucagon, and glucose. 226 87


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