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 change in plasma cyclic adenosine-3', 5'-monophosphate (AMP) was measured after intravenous injection of 1 mg of glucagon in 10 normal subjects and 30 patients with various forms of liver disease. Patients with cirrhosis and those with intrahepatic cholestasis responded normally but in patients with extrahepatic obstruction the plasma cyclic AMP response was considerably increased. Six of the eight patients with cirrhosis and a surgically created portacaval shunt had very reduced responses. This test may prove to be diagnostically important, particularly in differentiating surgical from non-surgical jaundice.
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PMID:Plasma cyclic adenosine-3', 5'-monophosphate response to glucagon in patients with liver disease. 17 99

Plasma cyclic AMP levels were determined during a 40 minute secretin infusion (1 Cl.U kg-1h-1) followed by a 40 minute combined secretin (1 Cl.U kg-1h-1) caerulein (75 ng kg-1h-1) infusion. In nine healthy subjects, both secretin alone and secretin in combination with caerulein did not affect plasma cyclic AMP levels. The same was observed in six patients with chronic pancreatitis. By contrast, in patients suffering from liver disease (nine cases) or extrahepatic cholestasis (six cases), secretin elicited large increases in plasma cyclic AMP concentration; the mean values attained being, respectively, seven and four times higher than before the infusion. On the other hand, increases in plasma cyclic AMP 10 minutes after a bolus injection of glucagon (1 mg) were four times lower in the liver disease group as compared to the controls. The results reported here suggest that the liver plays a major role in the degradation of plasma cyclic AMP produced by target tissues responding to secretin, and in the release of cyclic AMP under glucagon. Liver disease reduce the capacity of the liver to clear cyclic AMP from the blood. The pancreas does not contribute significantly to the cyclic AMP in the blood.
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PMID:Plasma cyclic AMP levels during a secretin-caerulein pancreatic function test in liver and pancreatic disease. 20 44

Plasma immunoreactive glucagon (IRG) was examined in volunteers with biopsy-proven cirrhosis of the liver after recovery from surgical portal--caval anastomosis. A wide range of increased total plasma IRG concentrations was found after overnight fast in groups of cirrhotic subjects with and without fasting hyperglycemia. Gel filtration chromatography of plasma showed a major component in the 3500-mol wt fraction in all cases so studied. Administration of glucose i.v. caused rapid suppression of total plasma IRG in normoglycemic and non-insulin-dependent hyperglycemic cirrhotic subjects. After administration of oral glucose, total plasma IRG was suppressed rapidly in normoglycemic cirrhotic subjects, while non-insulin-dependent hyperglycemic cirrhotic subjects exhibited delayed but prolonged suppression. Chromatography of selected plasma with glucose-suppressed total IRG showed a major decrease in the 3500-mol wt component in every case. Exaggerated increments of plasma gastric inhibitory polypeptide were demonstrable in both groups of cirrhotic individuals after administration of oral glucose, and it is speculated that this peptide may contribute to stimulation of glucagon secretion in liver disease associated with insulin deficiency.
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PMID:Hyperglucagonemia in liver cirrhosis with portal-systemic venous anastomoses: responses of plasma glucagon and gastric inhibitory polypeptide to oral or intravenous glucose in cirrhotics with normal or elevated fasting plasma glucose levels. 44 82

Porphyria cutanea tarda (PCT) has a known increased incidence of diabetes mellitus and hepatic involvement. We investigated glucose tolerance and glucoregulatory hormone alterations in seven patients with PCT and correlated these results with hepatic histology by percutaneous liver biopsy. Abnormal glucose tolerance was observed in six of the seven patients (87%). Fasting serum insulin levels were normal range, and normal glucose and growth hormone responses to standard, exogenous intravenous insulin were observed. Fasting serum glucagon and urine free cortisol levels were normal in those patients in whom they were measured. While varying degrees of abnormalities were found on histopathologic exam of the liver biopsies, no patient met the criteria for cirrhosis, and none of the patients demonstrated abnormal levels of insulin counterregulatory hormones commonly seen in cirrhosis. Thus, liver disease may not be the sole cause of the observed glucose intolerance and hyperinsulinemia in PCT patients.
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PMID:Carbohydrate metabolism in porphyria cutanea tarda. 46 44

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

The amylase/creatinine clearance ratio (Cam/Ccr ratio) was determined in 239 subjects. In 87 hospitalised patients without pancreatic disease (controls) the Cam/Ccr ratio was 3.02 +/- 0.69 (mean +/- ISD). The ratio was above the normal range in all patients with acute pancreatitis but was normal in those with chronic pancreatitis and carcinoma of the pancreas. In 18 patients with choledocholithiasis a raised ratio distinguished those with pancreatitis as assessed independently by the surgeon at laparotomy from those with a macroscopically normal pancreas. Raised Cam/Ccr ratios were also found in diabetics with ketoacidosis and in three patients with fulminant alcoholic liver disease. Though a positive correlation was found between the Cam/Ccr ratio and serum creatinine concentration, abnormally high ratios did not occur in 30 patients with chronic renal failure. A significant increase in Cam/Ccr ratios was produced in six healthy volunteers by intravenous injection of glucagon. However, it is unlikely that hyperglucagonaemia alone accounts for the increased Cam/Ccr ratio seen in acute pancreatitis, as no correlation was found between the clearance ratio and the plasma glucagon concentration in a series of patients. In two other patients in whom excess circulating pancreatic polypeptide was detected the Cam/Ccr ratio was normal. It is concluded that, in view of the sensitivity and relative specificity of finding an increased Cam/Ccr ratio in acute pancreatitis, its determination should be valuable clinically, especially in those cases of hyperamylasaemia where the cause is in doubt. The mechanism whereby the ratio is increased is unknown, and it is unlikely that either glucagon or pancreatic polypeptide is a major factor in its production.
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PMID:Mechanism and specificity of increased amylase/creatinine clearance ratio in pancreatitis. 60 90

Diabetes mellitus is more frequently found in pateints with hepatic cirrhosis (about 10%) than in subjects without liver disease. Cirrhosis has been the main subject of interest in this respect. Very few studies have been made in viral hepatitis or steatosis. In about 40% of cases, the diabetes is identified before the cirrhosis. More often (in about 60% of cases) the diabetes is discovered at the same time as or after the finding of cirrhosis. This "post-cirrhosis diabetes" shows no clinical peculiarity. In about 80% of patients with liver cirrhosis when fasting blood glucose is normal, abnormalities of carbohydrate metabolism are to be found by the oral glucose tolerance test. Approximately 50% show an abnormal response to intravenous glucose and 30% to intravenous tolbutamide. The "mechanism" of these metabolic abnormalities in liver cirrhosis is unknown. The following abnormalities are observed: 1) With similar glycaemic response to a glucose challenge, plasma insulin levels are higher than in patients without liver disease, suggesting insulin unresponsiveness. Resistance to exogenous insulin can be demonstrated. 2) Plasma free fatty acid levels are often elevated. 3) Plasma growth hormone levels are often raised. 4) Plasma glucagon levels are high when porto-caval shunting is present. 5) Potassium is often depleted. These metabolic abnormalities, in association with porto-caval shunting and hepatocyte insufficiency may explain the insulin resistance which characterises liver cirrhosis, and the diabetes which it may precipitate in predisposed persons.
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PMID:[Diabetes mellitus secondary to liver diseases. A review (author's transl)]. 79 27

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

Eighteen diabetic patients with lactic acidosis (L.A.) were analyzed for possible causal factors, metabolic changes, and efficacy of treatment. An antecedent phenformin therapy was performed in fifteen cases and was associated with renal insufficiency in ten cases and liver disease in eight cases. Tissular anoxia of primary hemodynamic or respiratory origin was absent in all cases. The severe metabolic acidosis (pH m.93 +/- 0,03; HCO3-= 6 +/- 1 MM; PaCO2 = 18 +/- 2 MM. Hg) and hyperlactatemia (14.2 +/- 0.3 mM) were associated with high lactate/pyruvate ration (70 +/- 22). High alanine levels (up to 4.6 mM) were measured in some of these patients. High beta-hydroxybutrate levels were sometimes measured (up to 7.6 mM), and substantial amounts of acetoacetate were also detected in twelve cases. Glucagon level was always increased (1,050 +/- 240 pg./ml.), and insulin/glucagon ratio was low. Cortisol (49 +/- 10 mug./100 ml.) and HGH (10.8 +/- 0.6 ng./ml.) were also elevated. Increased plasma levels of phenformin were measured in five L.A. diabetic subjects (50 +/- 5 mug./ml.) by comparison with other phenformin-treated diabetic subjects. The specificity of the assay was investigated, and phenformin metabolites were characterized by thin-layer chromatography. Por the treatment of L.A., adjunction of dialysis and furosemide improved the efficacy of early and massive sodium bicarbonate infusion. It is suggested that accumulation of phenformin via renal insufficiency plays a determinant role in causing L.A. through an impairment of lactate metabolism in the liver. An accelerated epuration of the drug may be helpful in therapy of L.A. Phenformin treatment should be avoided in case of renal and/or liver insufficiency.
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PMID:Phenformin-induced lactic acidosis in diabetic patients. 80 37

A 76-year-old man presented with hypoglycemic coma associated with metastatic liver disease. Serum immunoreactive insulin excluded insulinoma as a cause of hypoglycemia. Negative glucose responses to glucagon and epinephrine testing indicated failure of compensatory glycogenolysis. The patient's increased glucose requirements of 500 g per 24 hr were reduced to normal only after shrinkage of the liver tumor bulk was accomplished with chemotherapy. Hepatic hypoglycemia is discussed and the literature is reviewed.
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PMID:Hypoglycemia secondary to metastases to the liver. A case report and review of the literature. 83 May 86


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