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)

Perfusion of ischemic tissue with glucose has been shown to be deleterious to heart, spinal cord, and kidney. Observations that glucagon improves survival after acute mesenteric ischemia, however, suggest that hyperglycemia may not be deleterious during bowel ischemia. This experiment examined the effect of glucose infusion on survival in an established rat model of acute mesenteric ischemia. The superior (cranial) mesenteric artery (SMA) was occluded for 85 min in 36 anesthetized Sprague-Dawley rats. Animals were randomized to receive 5% glucose in normal saline (n = 15; 16.5 mL/kg.min iv), normal saline alone (n = 13; 16.4 mL/kg.min iv), or no intravenous fluid (n = 8). Ninety-minute intravenous infusions were initiated 10 min after SMA occlusion. Survival to 48 h was 47% in glucose-saline-treated rats, 31% in saline-only-treated rats, and 12.5% in control rats. These results demonstrate no deleterious effect of glucose infusion on mortality after acute mesenteric ischemia in this model.
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PMID:The effect of glucose infusion on survival after acute mesenteric ischemia/reperfusion. 228 46

Vasoactive agents, including glucagon, have been used in treatment of mesenteric ischemia. Such drugs change both intestinal blood flow and metabolism. Since reperfusion injury reflects the metabolic state of an organ as well as the duration and severity of ischemia, we investigated the effect of glucagon in a standard model of intestinal ischemia. Data were generated from denervated isoperfused rat small intestinal preparations (n = 39). Arterial and venous pressures, intestinal blood flow, and oxygen consumption were monitored. Animals were subjected to 15, 30, or 45 minutes of ischemia followed by 1 hour reperfusion. Experiments were performed without drug infusion or during intravenous glucagon administration (0.1, 0.2, or 0.4 micrograms/kg/min). After the rats were killed, histologic sections of intestine were graded 1 through 5 in a blinded fashion with 1 = normal villi and 5 = severe injury. Results (mean +/- SD) were analyzed by analysis of variance (*p less than 0.05). Glucagon at all concentrations increased intestinal blood flow and oxygen consumption before ischemia. For example, with 0.2 micrograms/kg/min glucagon, intestinal blood flow increased from 80.78 +/- 13.5 to 114.79 +/- 21.02 ml/min.100 gm* and oxygen consumption increased from 3.65 +/- 0.73 to 5.73 +/- 1.37 ml/min.100 gm.* Mucosal injury after ischemia reflected duration of ischemia and glucagon infusion rate. At all ischemic intervals, increased glucagon concentrations were associated with greater mucosal injury. In fact the histologic injury with 15 minutes of ischemia + 0.2 microgram/kg/min glucagon (3.04 +/- 0.49) exceeded that of 30 minutes of ischemia (2.87 +/- 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucagon potentiates intestinal reperfusion injury. 203 13

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.
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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

Exogenous fructose 1,6-diphosphate (FDP), a glycolytic intermediate, has recently been demonstrated to accelerate ATP production, prevent glycogen breakdown, stimulate glycogen synthesis, and synthesize free fatty acids in animals and humans. To assess the effects of FDP on the hormonal and metabolic response to exercise, ten trained males (34 +/- 7 yr) underwent 1 h of continuous exercise at 70% VO2max followed by 20 W.min-1 increments to exhaustion. Two hundred fifty mg.kg-1 body weight FDP or placebo was infused in randomized, double-blind, crossover fashion. No differences were observed in heart rate, blood pressure, gas exchange data, perceived effort, or glucose, insulin, free fatty acid, lactate, beta-hydroxybutyrate, glycerol, and glucagon concentration at rest, during exercise, or upon exhaustion. In contrast to the previously reported bioenergetic effects of FDP under conditions in which glycolysis is impeded (acidosis, hypoxia, and ischemia), FDP did not affect the gas exchange, hormonal, or substrate response to moderately high intensity exercise in healthy normals.
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PMID:Effect of fructose 1,6-diphosphate infusion on the hormonal response to exercise. 240 38

To assess the effects of xanthine oxidase (XO) inhibition on ischemic injury, rats were pretreated with oxypurinol (OXY, 5 mg/kg) and subjected to 30 min of bilateral renal artery occlusion. OXY's effect on adenine nucleotide-nucleoside-purine base concentrations was determined at 10 and 30 min of ischemia and during reperfusion (5 and 30 min). To assess whether XO-mediated oxidant stress influences the severity of ischemic acute renal failure (IARF), the effects of 1) OXY pretreatment and 2) hypoxanthine infusion were assessed. During ischemia OXY inhibited XO activity (more than fourfold rise in hypoxanthine-xanthine ratios) and induced quantitatively trivial but significant increases in ATP and total adenine nucleotide concentrations (by 30 min). Increased OXY dosage (15 mg/kg) or allopurinol (40 mg/kg) had no greater effects. At 5 min of reflow, OXY maintained XO inhibition but did not influence adenine nucleotide levels. By 30 min of reflow, 17-20% increments in ATP-total adenine nucleotides resulted. Nevertheless, OXY did not lessen the severity of IARF (assessed by azotemia-histology at 24 h). Hypoxanthine infusion increased end-ischemic hypoxanthine concentrations by 47%, but it did not change the severity of renal damage. Conclusions include 1) OXY-allopurinol induces intrarenal XO inhibition; 2) XO inhibitors slightly increase late ischemic-reperfusion adenine nucleotide concentrations; and 3) neither XO inhibition nor intrarenal hypoxanthine loading alters the severity of IARF, suggesting that XO-mediated oxidant stress is not a critical, consistent mediator of ischemic renal injury.
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PMID:Effects of xanthine oxidase inhibition on ischemic acute renal failure in the rat. 260 62

To study the effects of glucagon-insulin (G-I) infusion on protein synthesis and DNA synthesis in a condition with partial hepatic ischemia, G-I or saline was infused via portal vein for 40 minutes before and after a period of partial hepatic ischemia or following a period of partial hepatic ischemia. Protein synthesis was measured by 14C-leucine incorporation into proteins in incubated liver slices and DNA synthesis by 3H-thymidine incorporation into DNA. Protein synthesis in the postischemic liver was significantly recovered faster and more completely in G-I treated rats. G-I infusion enhanced the DNA synthesis of postischemic liver significantly, peaking 48 hours after the period of partial hepatic ischemia. However, the dosage of G-I infused in this investigation couldn't increase the hepatic tissue blood flow measured by hydrogen gas clearance method. On the histological examination, mitotic index was significantly higher in G-I treated group than in control. These results suggest that G-I infusion could be beneficial effects on the liver in situation with partial ischemic injury and that G-I infusion could remarkably augment hepatic tissue repair following ischemic damage.
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PMID:[Beneficial effects of glucagon-insulin infusion on hepatic protein synthesis and DNA synthesis in partial hepatic ischemia]. 267 61

The viability of the graft after liver transplantation is considered to be expressed as the sum of the hepatocellular activity by re-flowing of the hepatic blood flow after transplantation and the hepatocellular injury derived from the cold ischemia of the liver which is indispensable for transplantation. In order to elucidate the hepatocellular injury in ischemic liver graft cold ischemic liver model without hepatectomy was prepared and liver functions, serum insulin, glucagon and cyclic AMP after glucagon loading were measured. The following results were obtained. 1) Influence of anoxia due to ischemia of the liver expressed by s-GOT, disappeared 2 days after operation but it lasted for long time by s-GPT. Re-elevation of s-GOT, s-GPT observed after 2 days or more was considered to be derived from the hepatocellular necrosis due to rejection. Incidentally, Al-phosphatase was useful for judging the rejection, but s-total bilirubin, s-total cholesterol and albumin were considered to be not useful as parameters for evaluating the viability of the graft. 2) The rejection and the hepatocellular necrosis had not influence on serum insulin, but serum glucagon corresponded to the hepatocellular necrosis and was useful index for the judgment of the hepatocellular damage in the graft. 3) The level of c-AMP after glucagon loading and the c-AMP response corresponded very well to the hepatocellular activity of the graft, and they were considered to be useful indices for evaluating the viability of the graft.
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PMID:[Experimental study of orthotopic liver transplantation in dog--with reference to change of hepatic function, serum insulin, glucagon, c-AMP after liver transplantation and the viability of the graft]. 284 4

1. Ischaemia was applied for 30 min to the liver of Wistar rats and of gsd/gsd rats, which have a genetic deficiency of phosphorylase kinase. The rate of glycogenolysis corresponded closely to the concentration of phosphorylase a. The loss of glycogen from Wistar livers was accounted for by the intrahepatic increase in glucose plus lactate. Further, the accumulation of oligosaccharides was negligible in the gsd/gsd liver. 2. Isolated hepatocytes from Wistar and gsd/gsd rats were incubated for 40 min in the presence of either KCN or glucagon. Again, the production of glucose plus lactate was strictly dependent on the presence of phosphorylase a. However, the catalytic efficiency of phosphorylase a was about 2-fold higher in the presence of KCN. 3. We conclude that the hepatic glycogenolysis induced by anoxia and by KCN is solely mediated by phosphorylase a. The higher catalytic activity of phosphorylase a under these circumstances could be due to an increased concentration of the substrate Pi.
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PMID:The hepatic glycogenolysis induced by reversible ischaemia or KCN is exclusively catalysed by phosphorylase a. 322 40

This study assessed the contribution of angiotensin II, oxygen-free radicals, and vasopressin to the mortality of acute mesenteric ischemia in rats. Rats received saline replacement (16 ml/kg/hr) for 3 hr during and after 85 min of superior mesenteric artery (SMA) occlusion. Only 21% of rats that received saline alone (n = 14, control) survived 48 hr, significantly less than the 100% survival of sham-operated rats (no SMA occlusion, n = 5, P less than 0.01). Neither teprotide (an angiotensin converting-enzyme inhibitor), allopurinol (to reduce oxygen-free radical formation), nor a specific vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethyleneproprionic acid), 2-(O-methyl) tyrosine arginine-vasopressin] improved 48-hr survival, which was 17% in each group (n = 6, each). Survival improved significantly to 86% (n = 7, P less than 0.001) when intravenous glucagon (1.6 micrograms/kg/min) was given for 2 hr after SMA reperfusion. Survival after dopamine infusion (12 micrograms/kg/min iv) was 67% at 48 hr, a nearly significant improvement (n = 9, P less than 0.06). These results suggest that angiotensin II, oxygen-free radicals, and vasopressin do not contribute significantly to the high mortality observed after acute intestinal ischemia in this rat model, but that glucagon, and to a lesser extent, dopamine, are potentially therapeutic.
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PMID:Pharmacologic treatment of occlusive mesenteric ischemia in rats. 337 18

Endotoxemia is a frequent complication of many health disorders. It is characterized by systemic release of a variety of endogenous inflammatory mediators which effect cardiovascular depression, reductions in organ blood flow, tissue ischemia and derangements in cellular metabolism leading to death. During a continuous intravenous infusion of Escherichia coli lipopolysaccharide, the chronology of alterations in hepatosplanchnic blood flow, hepatic carbohydrate metabolism and pancreatic insulin secretion has been studied in awake Yucatan miniature pigs (Sus scrofa). Endotoxic shock in this model is characterized by reductions in portal venous and hepatic arterial blood flow, early transient increases in pancreatic insulin secretion, increases in the 3H-glucose-derived rates of glucose appearance and disappearance, profound hypoglycemia, hyperlactatemia and metabolic acidosis. Reductions in hepatic oxygen delivery are compensated for by enhanced oxygen extraction efficiency, but hepatic gluconeogenesis continues at an inadequate rate to compensate for increased glucose utilization. Experimental therapies including lidocaine, naloxone, captopril, dichloroacetate and glucagon each effect specific improvements in cardiovascular or metabolic function, but none significantly alter the composite derangements responsible for lethality in this model.
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PMID:Endotoxemia in Yucatan miniature pigs: metabolic derangements and experimental therapies. 353 41


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