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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic encephalopathy (H.E.) is associated with and perhaps caused by changes in plasma-aminoacid patterns--decreased branched-chain aminoacids (B.C.A.A.) and increased aromatic aminoacids (A.A.A.). The decreased B.C.A.A. may be in part secondary to hyperinsulinaemia, but the B.C.A.A. are catabolised by both fat and muscle. The increase in A.A.A. may reflect a "catabolic stimulus" reflected in hyperglucagonaemia, particularly in severe hepatic failure and H.E., and a decreased insulin/glucagon ratio. Endogenous protein, lean body-mass, or liver then releases large amounts of A.A. and the A.A.A. cannot be catabolised by the failing liver, and thus accumulate in the circulation. With decreased plasma-B.C.A.A., the molar ratio of B.C.A.A. and A.A.A. decreases allowing the toxic A.A.A. to penetrate the blood-brain barrier in increased amounts and encephalopathy develops. Appropriate therapy for H.E. must include reversal of the "catabolic state" by providing sufficient B.C.A.A. and calories to decrease the flux of A.A.A. from muscle and liver, and the restoration of the normal molar ratio of B.C.A.A. and A.A.A.
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PMID:Insulin, glucagon, aminoacid imbalance, and hepatic encephalopathy. 6 15

It is proposed that hyperammonaemia in liver cirrhosis or after portacaval shunt contributes to plasma neutral aminoacid imbalance and to increased activity of the blood-brain neutral amino-acid transport system. Plasma neutral aminoacid concentrations are deranged, partly, but not completely, because ammonia stimulates glucagon secretion; a high rate of gluconeogenesis and hyperinsulinaemia follow. Brain uptake of neutral aminoacids rises because ammonia stimulates brain-glutamine synthesis, which results in rapid exchange of brain glutamine for plasma neutral aminoacids. Hyperammonaemia therefore contributes to encephalopathy indirectly, by raising the brain concentration of neutral aminoacids which after neurotransmitter metabolism, rather than directly, by toxic effects on neuronal metabolism.
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PMID:Hyperammonaemia, plasma aminoacid imbalance, and blood-brain aminoacid transport: a unified theory of portal-systemic encephalopathy. 9 Aug 64

Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, beta-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids.
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PMID:Amino acid derangements in patients with sepsis: treatment with branched chain amino acid rich infusions. 9 98

A case of hyperinsulinism occuring in a newborn, with a birthweight of 4,050 g, is reported. The hypoglycaemia was refractory to the usual therapy (increase of glucose administration per os, and I.V., corticosteroids, glucagon, diazoxide). At surgery, undertaken at 9 days of age, an adenomatous nodule was removed along with the left part of the pancreas. Death occurred at 18 days, after the child had developed a transitory acidoketosic diabetes and an encephalopathy. Measurement of insulin by radio-immunoassay revealed a strong increase in the ratio insulin/glycaemia, characteristic of nesidioblastoma, as well as a high concentration of insulin in the tumor as compared to normal tissue. On the ultrastructural level, the observed features differed from those seen in children and adults and showed an abnormal overload of dense deposits in the cytoplasm of some histiocytes.
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PMID:[Islet cell adenoma with neonatal onset. Clinical, hormonological and ultrastructural study of a case]. 19 46

Alterations in insulin and glucagon levels might account for the plasma amino acid imbalance of cirrhotics. In order to verify this hypothesis we evaluated basal insulin, glucagon, branched-chain amino acids, aromatic amino acids, and free tryptophan in 13 controls and 37 cirrhotics divided on the basis of their mental state; in 4 patients the hormonal and amino acid patterns were sequentially studied during various stages of encephalopathy. Glucagon is high in cirrhotics and progressively increases with the worsening of the mental state. Free tryptophan and aromatic amino acids show a similar behavior and significantly correlate with glucagon levels (r = 0.67 and r = 0.81, respectively). On the other hand insulin levels, which are high in cirrhotics without encephalopathy, fall in the presence of deep coma. Insulin did not correlate with any of the plasma amino acids considered. Our data suggest that the catabolic state associated with increased glucagon levels may account for some of the alterations in the plasma amino acid profiles of cirrhotics. Portal-systemic shunting does not seem to be the common cause of both hyperglucagonemia and hyperaminoacidemia. Decreased branched-chain amino acid levels may be related to factors different from those involved in the alterations of carbohydrate homeostasis.
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PMID:Insulin and glucagon levels in liver cirrhosis. Relationship with plasma amino acid imbalance of chronic hepatic encephalopathy. 46 10

Blood substrate and hormone concentration were determined in 16 children with Reye syndrome prior to and following administration of hypertonic glucose. Baseline concentrations of lactate, pyruvate, alanine, glutamine, glutamate, proline, hydroxyproline, lysine, and aspartate were elevated (p less than 0.01), whereas citrulline and arginine were low. All substrate concentrations were below or within the normal range following 36 hours of therapy except those of lactate, pyruvate, and aspartate. Urea nitrogen excretion was reduced (p less than 0.05) on the second day of therapy. Plasma concentrations of insulin and growth hormone increased and glucagon decreased during the first day. Cortisol remained elevated throughout the study period. We conclude that the high circulating concentrations of substrates are the result of both increased mobilization and decreased clearance and that hypertonic glucose infusion suppresses substrate mobilization. A primary abnormality of the mitochondria could explain the metabolic perturbations that occurred. A possible relationship between the encephalopathy in this disorder and an insult to both brain and brain capillary mitochondria is discussed.
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PMID:Metabolic response to hypertonic glucose administration in Reye syndrome. 66 61

Alcoholic hepatitis presents as an acute hepatitis in an alcoholic. No specific laboratory tests for alcoholic hepatitis exist. Therefore, the diagnosis must be based on the clinical presentation, histology and exclusion of other causes of a similar clinical picture such as viruses and drugs. Patients with elevated bilirubin, encephalopathy and coagulopathy have a poor prognosis. Steroids, infusion of insulin and glucagon, supplementation of amino-acids and other experimental therapies do not appear to be helpful with the exception of steroids which may benefit the sickest patients. Long-term prognosis depends on the extent of cirrhotic changes present after the acute episode and on the drinking habits of the patient.
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PMID:[Alcoholic hepatitis]. 162 Dec 33

To study the effect of ammonia administration on amino acids and indoleamines in cerebrospinal fluid (CSF) and on amino acids, insulin, and glucagon in plasma in humans with liver cirrhosis, we performed seven ammonia tolerance tests on six patients with stable liver cirrhosis. The grade of encephalopathy was determined by psychometric tests. Only one of the patients had pronounced encephalopathy. The other patients had no or only slight encephalopathy. The plasma concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, and methionine decreased after the ammonia load, whereas no changes were found in the plasma concentrations of glucagon and insulin. In CSF the concentrations of glutamine, aromatic amino acids, and indoleamines increased only in the patient who had pronounced encephalopathy, whereas no changes were found in the other patients. The effect of an ammonia load on the concentrations of neutral amino acids in CSF in patients with pronounced encephalopathy remains to be demonstrated.
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PMID:The effects of ammonia tolerance tests on the cerebrospinal fluid concentrations of amino acids and indoleamines in patients with liver cirrhosis. 169 97

Severe alcoholic hepatitis is still a therapeutic challenge. It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate. A multicenter, randomized, single-blind, sequential trial was designed to compare this treatment with placebo. The triangular boundary was defined with alpha = 0.05, beta = 0.10 and estimated survival at 4 wk of 50% with placebo, 75% with treatment. Patients with biopsy-proven severe alcoholic hepatitis (presence of one or more of three criteria: encephalopathy, prothrombin activity less than or equal to 50%, bilirubinemia greater than or equal to 100 mumol/L) were randomized into two groups; one treatment group received an infusion (12 hr/day) of an association of insulin (30 IU) and glucagon (3 mg), and a control group received an infusion of glucose. Treatments were administered during a 3-wk period, and the mortality rate was noted at 4 wk. The decision to discontinue the trial was reached on the basis of results from the first 44 patients. Overall results were assessed in the 72 patients included at the time of this decision (treatment group: n = 37; control group: n = 35). Fifty-three patients had cirrhosis. No significant differences were noted between the two groups at inclusion on the basis of clinical, laboratory and histological criteria. The mortality rate was not significantly different in the two groups; 10 patients (27%) in the treatment group and 5 patients (14%) in the control group died. Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage, hepatic failure and infectious events.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of severe alcoholic hepatitis by infusion of insulin and glucagon: a multicenter sequential trial. 172 3

Alcoholic liver disease presents a wide spectrum of clinical manifestations ranging from mild asymptomatic fatty liver to alcoholic hepatitis and severe life-threatening liver failure with ascites, hemorrhaging esophageal varices, and encephalopathy. Although still poorly understood, the mechanism of this injury is probably the result of numerous direct toxic and metabolic effects of alcohol on the hepatocyte. Therapy consists primarily of abstinence and supportive care. However, several newer treatments are actively being studied. These include prednisolone, anabolic steroids, glucagon and insulin, propylthiouracil, and cyanidanol. Colchicine is promising as an agent to inhibit fibrosis. Complications of cirrhosis, including ascites and variceal hemorrhage, are the result of end stage disease. A return to old techniques of ascitic fluid management suggests that therapeutic large-volume paracentesis with albumin infusion is a safe and effective form of therapy. Variceal hemorrhage is best treated with sclerotherapy, vasoconstrictors, and balloon tamponade. Little has been done to alter the ultimately dismal prognosis and long-term survival of alcoholic liver disease.
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PMID:Alcoholic liver disease. 222 93


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