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 effect of liver disease on glucagon metabolism was examined in nine patients with chronic liver disease who were studied both before and after the creation of a surgical portasystemic shunt. Hepatocellular function did not deteriorate after shunt surgery. However, hepatic perfusion with splanchnic venous blood, as determined by scintisplenoportography, decreased after shunt surgery in six subjects but appeared unaltered in three. Basal plasma immunoreactive glucagon (IRG) levels in the pre-shunt cirrhotic group were significantly greater (p <0.005) than in control subjects and further increased (p <0.05) after shunt surgery. Moreover, the increase in basal IRG after shunt was evident only in patients in whom portasystemic shunting was demonstrably increased by surgery. Despite the higher basal IRG levels postoperatively, shunt surgery in the cirrhotics did not alter basal glucose and insulin levels or the glucose and insulin response to a glucose or protein load. Circulating IRG was heterogeneous in the pre-shunt cirrhotic patients: the 9000 molecular weight fraction comprised 27+/-4%, the 3500 mol. wt. fraction 71+/-4%, and the > 40 000 mol. wt. fraction was minimal. After shunt surgery, the relative proportion of the 9000 mol. wt. fraction of IRG (13+/-3%) decreased significantly (p <0.05) and this fall was associated with a corresponding increase in the 3,500 mol. wt. fraction (84+/-4%). It is concluded that, in cirrhosis, hyperglucagonaemia is: (1) dependent on the degree of portasystemic shunting rather than impaired hepatocellular function; (2) predominantly due to increased circulating 3500 molecular weight glucagon; and (3) not a major factor in the pathogenesis of carbohydrate intolerance in liver disease.
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PMID:Effect of portasystemic venous shunt surgery on hyperglucagonaemia in cirrhosis: paired studies of pre- and post-shunted subjects. 53 93

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

Previous studies suggested that hepatic alpha and beta adrenergic receptors is stable and it is in dynamic equilibrium under normal conditions. However, at a pathological condition these receptors may be changed. We studied the changes of adrenergic receptors in the rat liver with acute injury and in endotoxemia by light microscopic autoradiography. Our experimental results reveal that in the liver of rats with acute injury and in endotoxemia there were changes in varying degrees of alpha and beta adrenoceptors. Moreover, the changes were not uniform in various structures of the rat liver. Glucagon can keep adrenergic receptors stable on hepatic cells and muscular cells of blood vessels in the rat liver. Our experiment provides evidence for clinical use of adrenoceptor antagonists in the treatment of acute and chronic liver disease.
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PMID:Experimental studies on the changes of adrenergic receptors in rat liver with acute injury and in endotoxemia. 133 87

The poor prognosis of severe acute alcoholic hepatitis has stimulated interest in specific forms of treatment aimed at reducing the short term mortality as well as preventing progression to cirrhosis. Several controlled trials of steroid therapy have suggested an improvement in short-term survival, but the benefit seems to apply to highly selected cases only. Treatment with propylthiouracil and insulin and glucagon infusions has also shown promising results in controlled studies but there is still no general agreement on their value. Despite recent interest in the use of colchicine to prevent progression of cirrhosis in chronic liver disease of other aetiologies, its role in alcoholic liver disease is not yet clear. In end-stage alcoholic cirrhosis, excellent results are now being achieved with liver transplantation, although this is limited to patients who are not alcohol dependent and in whom there is no alcohol-induced extrahepatic disease.
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PMID:Treatment of advanced alcoholic liver disease. 187 84

Plasma insulin, glucagon, somatostatin, and glucose concentrations were measured in the fasting state as well as after mixed meals (breakfast, lunch, and dinner) in 10 cirrhotic patients and 10 control subjects during a 24-hour period. Cirrhotic patients had fasting glucose values higher than controls (at -15 min: 5.2 +/- 0.2 mmol/L v 3.9 +/- 0.5 mmol/L, P less than 0.05; at 0 min: 5.5 +/- 0.3 mmol/L v 4.3 +/- 0.5 mmol/L, P less than 0.01). After meals blood glucose values remained higher in cirrhotics than in controls. Insulin levels did not differ between the groups in the fasting state, but cirrhotics showed a lower response to meals. Corresponding glucagon concentrations were greater in cirrhotics than in controls before and after meals throughout the 24-hour period (from -15 min to 24 hour: P less than 0.01). BAsal plasma somatostatin levels in the cirrhotic group were significantly higher than in control subjects (at -15 min and at 0 min: P less than 0.05) and further increased after meals. Plasma somatostatin was heterogeneous in normal and cirrhotic group, but the increase in its concentrations in patients with chronic liver disease was for the most part a consequence of elevations in the 1600 and 3500 molecular weight components. The half-life of exogenously infused somatostatin in cirrhotics was comparable to that of controls. These results indicate that in liver cirrhosis elevated levels of circulating somatostatin are associated with hyperglucagonemia and impaired insulin release. The high plasma somatostatin levels observed in cirrhotic patients are the result of hypersecretion of the D cell rather than impaired removal of the peptide.
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PMID:Circulating somatostatin concentrations in healthy and cirrhotic subjects. 286 81

Portal hypertension is a common complication of chronic liver disease. Conventional therapy consists of surgery and palliative measures for the hemodynamic problem. It has been recently reported that somatostatin may reduce portal pressure without altering the systemic circulation and so reducing hepatic blood flow. This peptide also causes a significant fall in azygos circulation in patients with esophageal varices. The mechanism of this effect is unclear although suppression of intestinal vasodilating hormones and of glucagon have been claimed to play a role. Comparative clinical studies have shown somatostatin to be superior to the standard vasopressin treatment. Recent findings suggest that the efficacy of somatostatin can be increased by administering this peptide in repeated intravenous bolus injections. New derivatives, specially long-acting peptides, may eventually prove beneficial in the chronic treatment of this complication.
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PMID:Effects of somatostatin in patients with portal hypertension. 290 Feb 7

The effect of glucagon on hepatic regional hemodynamics was investigated in patients with chronic liver disease during peritoneoscopy with reflectance spectrophotometry. When glucagon was infused intravenously in patients with a non-cirrhotic liver, the regional hepatic tissue oxygen consumption, as estimated spectrophotometrically, increased significantly, whereas the index of hepatic tissue blood volume did not change appreciably, and consequently, the oxygen saturation of hemoglobin in the hepatic tissue blood decreased. In contrast, the administration of glucagon in patients with liver cirrhosis resulted in a significant increase in the index of hepatic tissue blood volume and produced a minor increase in hepatic tissue oxygen consumption. The oxygen saturation of hepatic blood hemoglobin tended to increase in the cirrhotics. The result suggests the presence of functional vasoconstriction at the presinusoidal and/or sinusoidal vessels in the cirrhotic liver, possibly due to a decreased vasomotor activity and/or an abnormal regulatory function of vasoactive substances, which are released by glucagon.
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PMID:Characterization of hepatic hemodynamics in cirrhotics and non-cirrhotics. Effect of glucagon infusion. 292 37

End-to-end portacaval transposition has previously been shown to produce less hepatocellular dysfunction than end-to-side portacaval shunt in the rat. Liver weight is also significantly reduced after portacaval shunt compared to portacaval transposition and these differences are not abolished by pair-feeding. Histological evidence of CNS damage is also reduced in transposed rats compared to shunted animals. This study examines the amino acid and hormone changes in these models. The characteristic amino acid changes of chronic liver disease (decreased branched-chain and elevated aromatic amino acids) are reproduced in portacaval shunt rats, but not in portacaval transposition. The differences between these groups in the branched-chain amino acids, but not those in the aromatic amino acids, are reduced by pair-feeding. Insulin and glucagon are elevated to a similar extent in both groups. These findings add further support to a role for peripheral amino acid imbalance in the pathogenesis of portal-systemic encephalopathy. Normal liver function, maintained by replacement of portal inflow with systemic blood, appears to minimize both CNS damage and amino acid changes.
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PMID:Amino acid imbalance following portal diversion in the rat. The relevance of nutrition and of hepatic function. 305 65

The role that portosystemic shunting plays in inducing the alterations of glucagon and insulin metabolism, which are observed in chronic liver disease, was studied in a rat model of prehepatic portal hypertension induced by portal vein constriction. Net splanchnic output of the hormones into the portal circulation was calculated from the difference between portal and systemic concentrations multiplied by portal plasma flow. Metabolic clearance rate was calculated as the ratio between output and systemic concentration. Portal blood flow was measured by the radioactive microsphere technique. Glucagon output in the portal vein-ligated rats was higher than in the sham-operated controls (5.9 +/- 1.5 vs. 2.0 +/- 0.2 ng/min, P less than 0.05). The metabolic clearance rate of glucagon was not significantly different between the two groups. Insulin output was not significantly different between the two groups; however, the metabolic clearance rate of insulin in the portal vein-ligated rats was reduced in comparison with the sham-operated group (9.5 +/- 1.5 vs. 18.4 +/- 3.3 ml/min, P less than 0.05). Our results indicate that portosystemic shunting per se is sufficient to cause an increased splanchnic output of glucagon into the portal system and a decreased metabolic clearance of insulin.
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PMID:Glucagon and insulin metabolism in a portal-hypertensive rat model. 330 69

In the present investigation, insulin sensitivity and fasting levels of insulin, C-peptide, glucagon, growth hormone and free fatty acids were estimated and correlated in a population of individuals suffering from liver cirrhosis or chronic hepatitis. Insulin sensitivity, assessed by glucose disappearance rate after intravenous bolus injection of insulin, was reduced but not significantly different from controls in subjects with chronic persistent hepatitis, while it was significantly reduced in individuals suffering from chronic active hepatitis or liver cirrhosis. Insulin, glucagon, growth hormone, and free fatty acid fasting levels were higher than in healthy subjects in individuals with liver cirrhosis or chronic active hepatitis but not in subjects with chronic persistent hepatitis. C-peptide concentrations did not differ from controls in subjects with liver disease. Significant negative correlations occurred between coefficients of insulin sensitivity and fasting concentrations of insulin, glucagon, growth hormone and free fatty acids, but not with fasting levels of C-peptide. Positive relationships were present between fasting levels of free fatty acids and both glucagon and growth hormone concentrations. These results show that, unlike subjects with liver cirrhosis and chronic active hepatitis, individuals suffering from chronic persistent hepatitis do not differ from healthy subjects in insulin sensitivity and fasting levels of insulin, glucagon, growth hormone, and free fatty acids. Moreover, they suggest that both hyperinsulinemia and high concentrations of counterregulatory substances might play a role in the pathogenesis of insulin resistance in subjects suffering from chronic liver disease.
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PMID:Possible roles of insulin, glucagon, growth hormone and free fatty acids in the pathogenesis of insulin resistance of subjects with chronic liver diseases. 639 73


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