Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucagon was tested for its effect on plasma adenosine 3',5'-cyclic monophosphate (cyclic AMP), insulin, and glucose in healthy subjects and in patients with advanced cirrhosis of the liver. In the normal subjects, intravenous infusion of glucagon caused a significant increase in plasma cyclic AMP, glucose, and insulin. In advanced cirrhotics, plasma cyclic AMP, glucose, and insulin did not increase. Adenylate cyclase concentration was measured in liver tissue from end stage cirrhotic patients and from brain-dead organ donors whose cardiovascular function was maintained in a stable state. Basal and total adenylate cyclase concentration were not different in the two groups. Adenylate cyclase from the livers of advanced cirrhotics was, however, significantly less responsive to glucagon stimulation than was that from donor livers. Hepatocytes in advanced cirrhosis have abnormal metabolic behavior characterized by abnormal adenylate cyclase-cyclic AMP response to hormonal stimulation.
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PMID:Cyclic AMP metabolism and adenylate cyclase concentration in patients with advanced hepatic cirrhosis. 21 45

The normal physiological role of glucagon is in controlling hepatic glucose output. Glucagon subserves the role of homeostasis by maintaining plasma glucose and of a stress hormone by producing hyperglycaemia. While control of glucagon release by circulating metabolites and also other hormones is clearly important, it seems likely that the nervous system exerts an over-riding influence. The parasympathetic nervous system maintains homeostasis and the sympathetic acts in stress. Glucagon levels are found to be high in cirrhosis and also after acute hepatic failure. It is likely that these changes in glucagon concentration are secondary to metabolic abnormalities. While some glucagon is cleared by the liver, a similar clearance is seen by many other tissues and it is not likely that the elevation of glucagon seen in liver failure is due solely to a gross deficiency of glucagon clearance. No liver abnormality is seen in the glucagonoma syndrome, where glucagon concentration are chronically high, or in patients who have had a total pancreatectomy, where plasma glucagon is undetectably low. It thus seems unlikely that liver mass is importantly controlled by glucagon.
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PMID:Signals for glucagon secretion. 24 99

Increased glucagon (IRG) levels have been documented in liver cirrhosis, particularly associated with portal-systemic shunting. In spite of increased insulin (IRI) levels, IRI/IRG are reduced. This alteration has been proposed to have a pathogenic role in plasma aminoacid imbalance which seems to account for hepatic encephalopathy. We studied IRG and IRI/IRG in 13 controls and in 3 groups of cirrhotics, divided on the basis of their mental state. Glucagon was determined by means of 30 K Unger's antibody; insulin by a double antibody technique. Results are expressed in the table as means +/- SEM. (Formula: see text)A progressive increase in IRG secretion is present in cirrhotics and correlates with the mental state; IRI/IRG is not altered in cirrhosis until neurological distrubances are present. A relative fall in IRI which can no more balance the increasing IRG values characterizes hepatic encephalopathy.
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PMID:The role of insulin and glucagon in the plasma aminoacid imbalance of chronic hepatic encephalopathy. 38 61

The present study was performed in order to evaluate the plasma glucose pattern in cirrhotic patients who, in the course of a continuous somatostatin infusion (500 microgram/h), were given pulses of glucagon (1 mg i.v.). In normal as well as in cirrhotic subjects somatostatin infusion provoked a marked reduction of the IRI plasma level and this was uninfluenced by subsequent glucagon administration. The rise in plasma glucose level in response to i.v. glucagon administration during somatostatin infusion was less marked in cirrhotics compared to normal subjects. This can be attributed to a variety of factors such as reduced number of liver cells or quantitative or qualitative changes of the liver cell glucagon receptors. Glucagon does not seem to contribute to the pathogenesis of carbohydrate intolerance in liver cirrhosis.
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PMID:Effect of somatostatin (SRIF) on plasma glucose and insulin response to glucagon in liver cirrhosis. 48 63

Glucagon is secreted not only by A2-cells of the pancreatic islets but also by A cells in the gastric fundus and duodenum. Several reports have demonstrated that the glucagon plasma concentration is increased in genetic diabetes as well as in many conditions associated with a decreased glucose tolerance such as hepatic cirrhosis, myocardial infarction, infectious diseases, burns, taumatic shock, glucagonomas, acute pancreatitis, acromegaly, pheochromacytoma and Cushing's syndrome. Hyperglucagonemia is particularly important in diabetic ketoacidosis and in non-ketotic hyperosmolar coma. The mechanisms responsible for the diabetic's hyperglucagonemia remain controversial. According to several authors, the increased glucagon secretion is, for its main part, secondary to a prolonged defect in insulin secretion and thus relatively insensitive to an acute insulin administration. According to others, the A cell abnormality is of primary origin, independant from insulin deficiency and its effects are cumulative with those of the insulin lack. Several reports dealing with induced or spontaneous experimental diabetes are in favor of the first or the second hypothesis. It appears likely that glucagon plays a role in the metabolic derangments of diabetes. Indeed, hepatic glucose production is closely related to the ratio of molar concentrations of insulin and glucagon. Finally, in insulin-dependant diabetics, somatostatin infusion reduces plasma glucagon concentration and blood glucose and prevents the development of ketosis after withdrawal of insulin therapy. These results illustrate the contribution of glucagon in the pathogenesis of hyperglycemia and ketosis. Several arguments have been accumulated in favor of the following concept: diabetes hyperglycemia results both from glucose under-utilization secondary to insulin lack and from hepatic glucose over-production due to glucagon excess. Although controversial, the role of glucagon in ketogenesis appears likely.
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PMID:[The role of glucagon in hyperglycemia. A review (author's transl)]. 79 28

Most forms of liver disease are probably associated with impaired gluconeogenesis, although hypoglycaemia is rarely an important clinical feature. Blood concentrations of the gluconeogenic precursors, lactate, glycerol and alanine are elevated although, in certain situations, alanine levels may be decreased. Abnormal glucose tolerance is present in both acute and chronic liver disease, but is usually not of clinical importance. The mechanism of glucose intolerance remains uncertain, with diminished hepatocyte mass, portal diversion and insulin resistance the major postulates. Indeed, the importance of the liver in disposing of an oral glucose load, is still questioned. Both hyperinsulinism and hypoinsulinism are found in liver disease, with hyperinsulinism common in cirrhosis and acute viral hepatitis. This is accompanied by insulin resistance. The hyperinsulinism is probably due to defective hepatic clearance of insulin rather that to over-production. The cause of the insulin resistance remains to be established. Glucagon levels are raised and may contribute to this resistance. Growth hormone levels are also increased but are associated with low somatomedin levels and the role of growth hormone in insulin resistance is therefore questionable. Future developments include use of new animal models, studies of biopsy specimens and studies of hepatic hormone receptors.
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PMID:Carbohydrate metabolism in liver disease. 79 84

Thioacetamide-induced rat cirrhosis was characterized by single-cell necroses, fibrosis, nodular parenchyma, decrease in parenchymal volume density and an increase in liver weight per body weight so that the total amount of parenchyma was not altered. The glycogen content was normal, and signs of decompensation were not found. Isolated livers were single-pass perfused by way of both the hepatic artery and the portal vein. In the normal livers stimulation of the nerve plexuses around the hepatic artery or portal vein (7.5 Hz; 2 msec) and infusions of noradrenaline (1 mumol/L) by way of either vessel and of acetylcholine (10 mumol/L) by way of the artery only increased glucose output, reduced both portal and arterial flow and increased the intravascular pressures. Glucagon (0.5 nmol/L) augmented glucose release and had no hemodynamic effects. In chronically thioacetamide-injured livers all stimuli caused smaller metabolic alterations per gram of liver weight and decreased portal flow more and arterial flow less with stronger enhancements of intravascular pressures than in the controls. The lowered metabolic responsiveness per gram of cirrhotic liver was largely compensated by the increase in liver weight. Thus despite massive histological alterations and pronounced increases in stimulation-dependent resistances - predominantly in the portal system - cirrhotic rat livers responded in their glucose metabolism to nervous and hormonal stimuli in almost the same manner as normal livers.
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PMID:Metabolic and hemodynamic responses of bivascularly perfused rat liver to nerve stimulation, noradrenaline, acetylcholine and glucagon in thioacetamide-induced micronodular cirrhosis. 154 28

The authors assessed in 12 patients with compensated cirrhosis of the liver, portal hypertension and oesophageal varices, using a Doppler flowmeter Toshiba SAL 50A/SDL 01 under basal conditions, changes in the width, rate of blood flow and blood flow though the trunk of the portal vein before and after intravenous administration of 1 mg glucagon. The width of the trunk of the portal vein did not change significantly during assessment. A statistically significantly increased flow through the portal vein was recorded starting during the 5th minute, and it correlated with the increased velocity of the blood flow. The increased flow persisted to the 20th minute after glucagon administration. The drop of pressure in a wedged position assessed in the hepatic veins after administration of the drug was not significant, the pressure in the free hepatic vein increased insignificantly. On the whole the portohepatic gradient declined by 10.5%, the drop was not significant. Glucagon in pharmacological doses has an early onset of action even in cirrhotic subjects whereby the increased flow through the portal vein does not lead to a rise of the portohepatic gradient. Glucagon administration thus does not increase the risk of haemorrhage from oesophageal varices during acute fibroscopy of the oesophagus and stomach in patients with portal hypertension.
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PMID:[The effect of glucagon on portal hemodynamics in patients with liver cirrhosis]. 202 94

The changes of humoral substances in the blood of cirrhotic rats were studied together with their effects on portal hemodynamics at different stages during the development of cirrhosis. The profiles of humoral substances and hemodynamics in two different cirrhotic rat models were also investigated. During the development of cirrhosis, glucagon increased markedly in all stages, histamine and vasoactive intestinal polypeptide (VIP) increased in the early stage, serotonin (5-HT) and somatostatin (SS) increased in the middle and late stages. There were different patterns of humoral substances in different cirrhotic models. Glucagon was the main humoral substance elevated in CCL4 induced cirrhosis, but histamine and 5-HT were mainly elevated in the blood in thioacetamide (TAA) induced cirrhosis. The hemodynamics altered differently in different stages during the development of cirrhosis and differently in the two cirrhotic rat models. Exchange transfusions between normal and cirrhotic rats resulted in an elevation of portal flow in normal rats, but no such changes were found after exchange pressure and an increase of portal blood transfusions between normal rats. The relationship between the humoral substances and portal hemodynamics is discussed. The results of this study strongly support the hypothesis of "humoral mechanism" in the pathogenesis of portal hypertension due to cirrhosis.
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PMID:Changes of blood humoral substances in experimental cirrhosis and their effects on portal hemodynamics. 212 49

Hepatic function frequently becomes worse, after hepatectomy in patients with hepatocellular carcinoma associated with cirrhosis. We usually use insulin and glucagon to treat patients with poor hepatic function, so we examined hepatic function in these patients in relation to bile acid metabolism. 1) Total serum bile acid levels were increased in patients with cirrhosis, and serum GCDCA, TCDCA values were especially high. After surgery, they rose even higher. 2) Glucagon was shown to stimulate C-AMP and decreased total serum bile acid, and especially serum GCDCA and TCDCA values.
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PMID:[Effect of glucagon on bile acid after hepatectomy in patients with hepatocellular carcinoma associated with cirrhosis]. 217 18


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