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)

A hepatic stimulator substance (HSS) was extracted from the liver of male weanling SD rats according to the method of LaBrecque. The mice were injected with carbon tetrachloride or D-galactosamine to induce hepatic injuries and the protective effect of HSS on thus induced hepatic damage was investigated. The results were as follows: (1) HSS could suppresses the elevation of sGPT and sGOT induced by carbon tetrachloride intoxication in a dose-dependent manner. (2) Hepatic histological findings indicated that the degree of CCl4 or D-galactosamine-induced hepatic lesions could be lessened by HSS. (3) CCl4-induced reduction of hepatic mitochondrial succinic dehydrogenase activity could be restored by HSS. (4) Insulin-glucagon enhanced the survival of D-galactosamine intoxicated mice and stimulated hepatocyte proliferation, thus showing less pronounced hepatic damage.
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PMID:[Protective effect of hepatic stimulator substance against experimental acute liver failure in mice]. 179 5

To assess the metabolic characteristics of cirrhotic hepatocytes, a primary culture of hepatocytes was established using rat liver induced cirrhosis by CCl4 administration. Using this system, cell responsiveness to different metabolic and excretory stimuli was investigated and compared with a primary culture of normal healthy rat hepatocytes. Cirrhotic hepatocytes showed reduced protein synthesis in response to insulin and reduced urea synthesis in response to glucagon. However, DNA synthesis stimulated by insulin and EGF was significantly enhanced in cirrhotic hepatocytes. No significant difference was observed in the fluorescein diacetate excretion rate. Cirrhotic hepatocytes showed impairment of antipyrine metabolism and conjugation and excretion of unconjugated bilirubin. These results suggest indirectly that cirrhotic hepatocytes may be less functionally mature than normal healthy hepatocytes.
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PMID:[Studies on metabolic characteristics of cirrhotic rat hepatocytes using primary culture]. 221 64

In order to pinpoint the site causing increased intrahepatic vascular resistance, we observed the relationship between hepatic pathologic changes and free portal pressure (FPP) during the development of CCl4-induced liver cirrhosis of rat. The results suggested that the degeneration necrosis and regeneration of liver cells, and consequent stenosis, or obliteration of sinusoidal spaces caused by the swelling and disarrangement of the liver cell plates led to the occurrence of portal hypertension. The possibility of pre- or post-sinusoidal obstruction was excluded by the manifestation of the pathologic lesions. It is the authors' belief that the exact site of the increased intrahepatic vascular resistance was most likely at the level of hepatic sinusoids. Furthermore, there was certain positive correlation between plasma glucagon concentration and FPP, indicating that glucagon was also involved in the pathogenesis of portal hypertension.
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PMID:[Relation of hepatic pathologic changes and portal venous pressure in the course of cirrhosis in rats]. 237 24

The change of humoral substances in the blood of cirrhotic rat was studied at different stages of development, together with their effects on the portal hemodynamics. The profiles of humoral substances and hemodynamics in two different cirrhotic rat models, as well as the changes of portal hemodynamics in the normal rats after perfusion with the arterial blood from cirrhotic rats were also investigated. It was found that: during the development of cirrhosis, glucagon increased markedly at all stages, histamine and vasoactive intestinal polypeptide (VIP) increased at early stage only, while serotonin (5-HT) and somatostatin(SS) increased at middle and advanced stages. In the CCl4 induced cirrhosis, glucagon was the main humoral substance, whereas in the thioacetamide (TAA) induced cirrhosis, histamine and 5-HT were mainly elevated. The portal hemodynamics altered differently in different stages during the development of cirrhosis and in the two different cirrhotic rat models. The perfusion with the arterial blood from cirrhotic rats caused an increase of portal venous pressure and portal venous flow in normal rats.
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PMID:[Changes in humoral substances in induced cirrhosis and their effects on portal hemodynamics]. 257 72

The incubation of isolated rat hepatocytes with 0.172 mM carbon tetrachloride caused a rapid decrease in the calcium content of both mitochondrial and extramitochondrial compartments. However, the release of Ca2+ from the intracellular stores was not associated with an increase in the cytosolic Ca2+ levels as measured by activation of phosphorylase alpha or by Quin-2 fluorescence. A rapid rise in hepatocyte free calcium was only observed with concentrations of CCl4 higher than 0.172 mM. The lack of activation of phosphorylase alpha was not due to the inhibition of the enzyme by CCl4, since in CCl4-treated hepatocytes the phosphorylase activity could be stimulated by glucagon, butyryl--cAMP or by the increase of cell calcium induced by the addition of A23187. Ca2+-dependent ATPase of plasma membranes was only slightly affected in the early phases of poisoning with CCl4 when both mitochondrial and extramitochondrial calcium pools were already lowered. This led to the conclusion that calcium released from intracellular organelles could be extruded from the cells in sufficient amounts to prevent the increase of the cytosolic levels. A rise in hepatocyte free calcium was observed during the second hour of incubation with CCl4, concomitantly with the appearance of both LDH leakage and plasma membrane blebbing. The addition of EGTA to the medium prevented both the increase in cytosolic Ca2+ and the blebbing suggesting that they were a consequence of an influx of calcium into the cells. However, neither EGTA nor the addition of inhibitors of calcium-dependent phospholipase A2 or non-lysosomal proteases were able to protect against cell death. These latter results suggested that the alterations of calcium distribution induced by CCl4 in isolated hepatocytes were not a primary cause of the toxic effects, although they did not exclude that a sustained rise in cytosolic Ca2+ could contribute in the progression of cell injury.
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PMID:Effects of carbon tetrachloride on calcium homeostasis. A critical reconsideration. 276 92

The effects of 8-(2-dimethylaminoethyl)-3-oxo-4-phenyl-1-thia-4,8-diazaspiro [4, 5] decane dihydrochloride monohydrate (Y-8845) on carbon tetrachloride (CCl4)-induced liver injury were investigated in rats. CCl4-induced attenuation of the plasma cyclic AMP (cAMP) response to glucagon stimulation was significantly prevented by pretreatment with Y-8845. Y-8845 also effectively suppressed the increases in the activities of serum transaminases as well as the decreases in microsomal glucose-6-phosphatase activity and microsomal cytochrome P-450 concentrations induced by CCl4. In rats at 72 hr after CCl4 administration, the plasma cAMP response to glucagon, microsomal glucose-6-phosphatase activity and P-450 concentration were all below the control level. Y-8845 treatment after CCl4 administration rectified these reductions to nearly normal levels. Furthermore, Y-8845 stimulated DNA synthesis during liver regeneration after CCl4 intoxication. These results demonstrate that Y-8845 has a protective effect against CCl4-induced injury in the liver and a stimulating effect on the recovery of the damaged liver.
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PMID:Effects of 8-(2-dimethylaminoethyl)-3-oxo-4-phenyl-1-thia-4,8-diazaspiro [4,5] decane dihydrochloride monohydrate (Y-8845) on carbon tetrachloride-induced liver injury. 301 90

Rats given a dose of carbon tetrachloride (CCl4) immediately received injections of glucagon and insulin every 4 h. They frequently died after 4 h and showed a significantly higher mortality between 8 h and 28 h as compared to the control rats where such deaths occurred 16 h later. At 8 h, the derangements of SGPT values and prothrombin time were significantly greater in the hormone-treated rats than in the control rats. In these CCl4-intoxicated rats, hepatic reduced glutathione content at 4 h was significantly reduced after hormone treatment. The treatment significantly enhanced CCl4 metabolism, conversion of 14CCl4 into 14CO2 in vitro, by microsomes isolated from the liver, whereas it did not affect the microsomal cytochrome P450 content. These results suggest that glucagon and insulin treatment increased CCl4 hepatotoxicity in rats through activating the cytochrome P450-dependent mono-oxygenase system. This would merit consideration for the clinical application of this treatment.
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PMID:Enhancement of carbon tetrachloride-induced liver injury by glucagon and insulin treatment. 328 Nov 98

The release of insulin and glucagon in cirrhotic rats was examined. Rats were made cirrhotic by a combination treatment of carbon tetrachloride (CCl4) and phenobarbitone. Liver cirrhosis was verified by histologic findings. Both basal and stimulated release of insulin from isolated pancreatic islets, in vitro, were decreased significantly in cirrhotic rats, as compared with control rats. Basal, but not stimulated, levels of glucagon, in vitro, were reduced significantly in cirrhotic rats. Circulating levels of plasma insulin, glucagon, glucose, bilirubin, and amylase levels were unaffected in cirrhotic rats when compared with control rats. There were no signs of pancreatitis. The results indicated that the release of insulin and glucagon is depressed in cirrhotic rats and in rats treated with phenobarbitone and CCl4. Clearance of circulating insulin and glucagon by the liver was apparently reduced, since circulating levels of insulin and glucagon were unaltered in all treated rats.
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PMID:Insulin and glucagon production in experimental cirrhosis. 354 4

Mechanisms of glycogenolysis have been investigated in a comparative study with Wistar rats and gsd rats, which maintain a high glycogen concentration in the liver as a result of a genetic deficiency of phosphorylase kinase. In Wistar hepatocytes the rate of glycogenolysis, as modulated by glucagon and by glucose, was proportional to the concentration of phosphorylase a. In suspensions of gsd hepatocytes the rate of glycogenolysis was far too high as compared with the low level of phosphorylase a; in addition, only a minor fraction of the glycogen lost was recovered as glucose and lactate, owing to the accumulation of oligosaccharides. When the gsd hepatocytes were incubated in the presence of an inhibitor of alpha-amylase (BAY e 4609) glycogenolysis and the formation of oligosaccharides virtually ceased; the production of glucose plus lactate, already modest in the absence of BAY e 4609, was further decreased by 40%, owing to the suppression of a pathway for glucose production by the successive actions of alpha-amylase and alpha-glucosidase. Evidence was obtained that gsd hepatocytes are more fragile, and that amylolysis of glycogen occurred in damaged cells and/or in the extracellular medium. This may even occur in vivo, since quick-frozen liver samples from anesthetized gsd rats contained severalfold higher concentrations of oligosaccharides than did similar samples from Wistar rats. However, administration of a hepatotoxic agent (CCl4) caused hepatic glycogen depletion in Wistar rats, but not in gsd rats. The administration of phloridzin and of vinblastine, which have been proposed to induce glycogenolysis in the lysosomal system, did not decrease the hepatic glycogen level in gsd rats. Taken together, the data indicate that only the phosphorolytic degradation of glycogen is metabolically important, and that alpha-amylolysis is an indication of an increased fragility of gsd hepatocytes, which becomes prominent when these cells are incubated in vitro.
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PMID:An assessment of the importance of intralysosomal and of alpha-amylolytic glycogenolysis in the liver of normal rats and of rats with a glycogen-storage disease. 387 83

The effects of insulin, glucagon, isoproterenol and carbachol on the regeneration of injured liver were investigated in rats treated with carbon tetrachloride (CCl4). These agents effectively potentiated hepatic DNA synthesis in rats both at 48 and at 72 hr after CCl4 intoxication. The maximal stimulatory effects of the agents on the synthesis coincided in time with the peak of elevation in basal DNA synthesis following the intoxication. Plasma levels of insulin and triiodothyronine were decreased before the elevation of basal DNA synthesis in CCl4-treated rats. The possible relationship of these changes in plasma hormones to the potentiated effects of the agents on DNA synthesis was examined in rats treated with streptozotocin (STZ) or methylthiouracil (MTU). The agents caused no potentiation in STZ-treated rats. On the other hand, in MTU-treated rats, isoproterenol and carbachol significantly stimulated DNA synthesis, but this was not the case with insulin and glucagon. These results suggest that the pancreatic hormonal, beta-adrenergic and cholinergic stimulations play positive roles in regulating liver regeneration after CCl4 intoxication. Furthermore, the hypothyroid state developed in CCl4-treated rats may provide favorable conditions for the stimulation of DNA synthesis by isoproterenol and carbachol. It is unlikely, however, that insulin deficiency contributes to potentiations in the regenerative responses of the injured liver.
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PMID:Influence of plasma hormone levels on various stimulant-induced hepatic DNA synthesis in carbon tetrachloride-intoxicated rats. 388 87


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