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

Intravenous infusion of glucagon (100 micrograms/hr/100 g body weight) in rats produces a 20 to 35% increase in bile flow and enhances the activity of hepatic bilirubin uridine diphosphate-glucuronyltransferase to 132% after a 90 min infusion. When a bilirubin load is given to produce a constant and apparently maximal biliary bilirubin excretion rate (or transport maximum) the administration of glucagon increased the bilirubin transport maximum. The excretion rate of bilirubin monoglucuronides was more enhanced than that of diglucuronide. The enhanced rate of glucuronidation, assayed in vitro, correlated with the augmented biliary output and inversely with the plasma unconjugated bilirubin levels. It is concluded that glucagon, at the dosage used, leads to a higher formation rate of bilirubin monoconjugates and that the choleresis, also induced by the hormone, enhances the biliary secretion of the monoconjugates formed. The enhanced conjugation results in a decreased plasma concentration of unconjugated bile pigment and the associated choleresis leads to a decreased di- to monoconjugate ratio, opposite to what has been observed during bilirubinostasis and cholestasis. The secretory efficacy, as assessed from the bile-to-plasma concentration ratio, is enhanced for all bilirubin pigments after glucagon administration.
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PMID:Glucagon enhances bile flow, bilirubin uridine diphosphate-glucuronyltransferase activity and biliary bilirubin monoconjugate excretion in the rat. 130 Sep 45

The hepatic toxicity of TPN that is seen clinically appears to be multifactorial in origin. Most patients develop a combination of hepatic steatosis with evidence of cholestasis and abnormalities in liver function. The model that we have studied is one of pure hepatic steatosis since, on repeated study, these rats do not develop any liver function abnormalities. It is unclear whether this is related to the fact that these are short-term experiments, that rat livers respond differently from humans, or that rats do not have gallbladders. It has not been possible to carry these experiments out beyond 3 weeks since the rats develop bacterial colonization of the central lines as well as evidence of line sepsis. thus confounding the issue of hepatic toxicity being due to the TPN or to sepsis. One hypothesis is that hepatic steatosis is an early marker of liver toxicity and that prevention or reversal of hepatic steatosis may protect the liver from further abnormality. Insulin and glucagon seem to play a critical role in the development of TPN-associated hepatic steatosis. Specifically, an elevated portal venous insulin-glucagon molar ratio appears to be the primary stimulus and any treatment that lowers this ratio should diminish hepatic steatosis. The use of glucagon as a treatment modality is new. We have found no evident side effects of low dose glucagon in rats when it is added to the TPN solution. Glutamine has received much attention recently as a nutritional pharmacological agent in ameliorating some of the intestinal complications of parenteral nutrition and is well tolerated when administered appropriately. Intravenous lipid administration is an important nonprotein calorie source, especially when a high dextrose base cannot be used, and plays a role as well in preventing the development of hepatic steatosis. Thus, it is suggested that the clinical treatment of hepatic steatosis during TPN can be safely performed using any one, or a combination, of these modalities and without having to discontinue the TPN infusions. Since we observed no deterioration of liver function in rats receiving TPN for up to 2 weeks, we cannot completely relate these findings and recommendations to the hepatic dysfunction seen clinically with the use of TPN. Additional study will be required before this can be conclusively determined.
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PMID:Pathogenesis of hepatic steatosis during total parenteral nutrition. 190 28

Hepatic steatosis is one of the two principal hepatic complications of total parenteral nutrition (TPN), the other being cholestasis. While the cause is uncertain, an excess of carbohydrate calories in rats leads to an elevated portal insulin/glucagon (I/G) molar ratio, periportal fatty infiltration, and increased total hepatic lipid content. Insulin causes fatty acid biosynthesis, whereas glucagon causes hepatic release and inhibition of fatty acid synthesis. Thus we attempted to add glucagon to lower the I/G to see if this would affect the degree of hepatic fatty infiltration by encouraging hepatic fat mobilization. Adult rats (n = 21) received internal jugular catheters; Group 1 (n = 7) was given saline solution (3 ml/h) and chow ad libitum; Group 2 (n = 7), 25% dextrose-base (D25W) TPN solution; Group 3 (n = 7), D25W TPN + 33 micrograms/100 gm/day glucagon. At 7 days portal and peripheral venous blood samples were drawn for insulin and glucagon radioimmunoassay and blood glucose determination; livers were removed for histologic study and lipid determination. Blood glucose did not differ in any group. Hepatic lipid and peripheral and portal venous I/G were increased and periportal fatty infiltration was extensive in Group 2, whereas hepatic lipid and I/G were decreased and periportal fatty infiltration was absent in glucagon-infused rats (Group 3). An abnormally high I/G ratio in portal blood elicited by high-glucose TPN may be responsible, at least in part, for hepatic steatosis. By increasing hepatic lipid export, addition of glucagon to TPN may play a major role in decreasing hepatic steatosis.
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PMID:Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. 313 27

Surgical management of extrahepatic cholestasis is frequently complicated by sepsis, which can be explained in part by diminished function of the reticuloendothelial system. We have explored the possibility that the metabolic response to infection may also be abnormal. Fischer 344 rats underwent either bile duct ligation (BDL) or sham operation and were studied 3 days after operation. Hepatic amino acid uptake measured in vivo by the accumulation of 14C-alpha-aminoisobutyric acid or in vitro by the rate of transport of 14C-alanine by isolated hepatocytes was unaltered in the BDL animals, while gluconeogenesis from alanine by viable hepatocytes from BDL rats was actually enhanced. However, the expected increase in hepatic amino acid uptake in response to endotoxin was diminished in the BDL animals. In addition, we observed impaired responses of the jaundiced animals to glucagon and interleukin-1, two mediators of the hepatic acute phase response to endotoxin. These data suggest that while hepatic amino acid transport is normal in the basal state, the rat with extrahepatic biliary obstruction does not respond appropriately to stress and that this defect cannot be explained solely on the basis of altered handling of endotoxin by the reticuloendothelial system.
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PMID:Impaired metabolic response to endotoxin in obstructive jaundice. 352 8

A total pancreatectomy was performed in a 39-year-old man diabetic with diffuse calcification of the whole pancreas, a pseudocyst and intrapancreatic bile duct obstruction. The body of the excised pancreas was immediately transplanted into the left groin. The postoperative responses of plasma glucagon and insulin were not impaired compared with their preoperative responses. The patient was relieved of unremitting pain and is doing well six months after this operation.
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PMID:Segmental auto-transplantation of the pancreas. 355 85

Bile acids induce membrane alterations including reduced response to peptide hormones in vitro. Isolated liver cells from rats with bile duct obstruction were studied regarding gluconeogenesis and its hormonal control. While cells from shamoperated animals showed an 63% increase of glucose release in the presence of glucagon (1 microM), cells from cholestatic livers did not response regardless of the duration of obstruction. Cholestatic cells also showed other signs of membrane alterations, such as an increased enzyme leakage while redoxstatus and other metabolic responses were unchanged. These results suggest that a loss of hormonal control in the liver could contribute to disturbations of glucose homeostasis in cholestatic conditions.
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PMID:Loss of glucagon control of gluconeogenesis in liver cells from rats with bile duct obstruction. 397 8

One proposed mechanism for the cholestasis associated with total parenteral nutrition is infusion of amino acids. Arginine, 19 mumol/kg/min, was infused for a short time in healthy dogs with a biliary fistula to test the effect of endogenous hormone release on bile flow and composition. Both plasma glucagon and blood glucose levels increased. Despite the release of the choleretic hormone, glucagon, bile flow decreased 30%. The suppression of bile flow was attributed to a decrease in the bile acid-dependent fraction of bile flow. Bile acid, cholesterol, and phospholipid output were all depressed.
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PMID:Inhibition of bile flow by intravenous arginine hydrochloride. 403 68

Following an intravenous bolus of 1 mg glucagon plasma level time profiles of glucagon, cyclic AMP and glucose were monitored for two hours in 6 healthy adult volunteers, 6 patients with decompensated cirrhosis, 6 patients with acute viral hepatitis and at recovery, 6 patients with extrahepatic and 4 patients with intrahepatic cholestasis. Elimination half-livers of glucagon (controls = 22.5 +/- 5.6 min) were significantly prolonged in patients with cirrhosis (52.2 +/- 30.8 min) amd acute hepatitis (58.6 +/- 26.3 min). The glucagon - induced rise in cyclic AMP was similar in all subjects but independent of the phase of the hepatitis (acute or recovery) maximal cyclic AMP values were significantly higher in those patients compared to controls. In contrast glucose response was much lower (p less than 0.001) in patients with hepatitis (acute and recovery). All measured parameters, demonstrated considerable individual variations and a large overlap between the different groups of subjects. Therefore it is concluded that these observations negate the diagnostic and functional usefulness of the glucagon test as a predictive liver function index.
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PMID:Glucagon-induced alterations of plasma levels of cyclic AMP and glucose in patients with liver disease. 632 1


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