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)

After the infusion of fructose, 0.25 g/kg body weight, blood uric acid levels were significantly increased above the mean basal value in five patients with glycogen storage disease (GSD), type I (P less than 0.02-P less than 0.05). The mean fasting blood inorganic phosphate (Pi) level in the patients was 3.9 +/- 0.3 mg/100 ml and was significantly lower than the mean Pi value of 4.8 +/- 0.3 mg/100 ml of the control subjects (P less than 0.05). Blood Pi levels were significantly lower in the patients than in the control subjects at varying times after the administration of fructose (P less than 0.005-P less than 0.05). Uric acid excretion did not increase significantly in the patients after fructose was given. In contrast to normal children, the mean peak blood uric level in the patients increased significantly after the administration of glucagon (P less than 0.001). In both patients (P less than 0.005) and control subjects (P less than 0.05), mean blood Pi concentrations decreased significantly after the administration of glucagon; however, the blood Pi concentrations in the patients were significantly lower than in the control subjects. Uric acid excretion increased after glucagon administration in both patients and control subjects, but the differences in uric acid excretion between the two groups were not significant. The data in our patients after fructose and glucagon administration suggest that hyperuricemia in GSD results from enhanced nucleotide catabolism. The concentrations of hepatic Pi and ATP may be low in patients with GSD; hepatic Pi and ATP content would therefore be further diminished by the administration of fructose and glucagon. By a mechanism similar to that of fructose-induced hyperuricemia, diminished hepatic Pi and ATP content might increase the breakdown of adenine nucleotides with resultant hyperuricemia.
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PMID:The pathogenesis of hyperuricemia in glycogen storage disease, type I. 26 62

Other investigators have shown that fructose infusion in normal man and rats acutely depletes hepatic ATP and P(i) and increases the rate of uric acid formation by the degradation of preformed nucleotides. We postulated that a similar mechanism of ATP depletion might be present in patients with glucose-6-phosphatase deficiency (GSD-I) as a result of ATP consumption during glycogenolysis and resulting excess glycolysis. The postulate was tested by measurement of: (a) hepatic content of ATP, glycogen, phosphorylated sugars, and phosphorylase activities before and after increasing glycolysis by glucagon infusion and (b) plasma urate levels and urate excretion before and after therapy designed to maintain blood glucose levels above 70 mg/dl and thus prevent excess glycogenolysis and glycolysis. Glucagon infusion in seven patients with GSD-I caused a decrease in hepatic ATP from 2.25 +/- 0.09 to 0.73 +/- 0.06 mumol/g liver (P <0.01), within 5 min, persisting in one patient to 20 min (1.3 mumol/g). Three patients with GSD other than GSD-I (controls), and 10 normal rats, showed no change in ATP levels after glucagon infusion. Glucagon caused an increase in hepatic phosphorylase activity from 163 +/- 21 to 311 +/- 17 mumol/min per g protein (P <0.01), and a decrease in glycogen content from 8.96 +/- 0.51 to 6.68 +/- 0.38% weight (P <0.01). Hepatic content of phosphorylated hexoses measured in two patients, showed the following mean increases in response to glucagon; glucose-6-phosphate (from 0.25 to 0.98 mumol/g liver), fructose-6-phosphate (from 0.17 to 0.45 mumol/g liver), and fructose-1,6-diphosphate (from 0.09 to 1.28 mumol/g) within 5 min. These changes, except for glucose-6-phosphate, returned toward preinfusion levels within 20 min. Treatment consisted of continuous intragastric feedings of a high glucose dietary mixture. Such treatment increased blood glucose from a mean level of 62 (range 28-96) to 86 (range 71-143) mg/dl (P <0.02), decreased plasma glucagon from a mean of 190 (range 171-208) to 56 (range 30-70) pg/ml (P <0.01), but caused no significant change in insulin levels. Urate output measured in three patients showed an initial increase, coinciding with a decrease in plasma lactate and triglyceride levels, then decreased to normal within 3 days after treatment. Normalization of urate excretion was associated with normalization of serum uric acid. We suggest that the maintenance of blood glucose levels above 70 mg/dl is effective in reducing serum urate levels and that transient and recurrent depletion of hepatic ATP due to glycogenolysis is contributory in the genesis of hyperuricemia in untreated patients with GSD-I.
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PMID:ATP depletion, a possible role in the pathogenesis of hyperuricemia in glycogen storage disease type I. 27 29

The acute hormonal and amino acid responses to differing food substrates were examined in type 1 glycogen storage disease. Ingestion of a glucose load or a glucose-plus-beef meal caused an acute fall in the initially elevated plasma glucagon, alanine, proline, and lactate. Ingestion of beef alone caused a sharp rise in these parameters. Long term nocturnal intragastric therapy of a high carbohydrate and moderate amino acid content resulted in a similar fall in these parameters as well as a fall in the elevated plasma glutamate, uric acid, triglycerides, and RBC-reduced glutathione. A remarkable clinical improvement and growth spurt accompanied the improvement in these biochemical values. The possible relation between the disturbed plasma hormonal and amino acid findings and growth failure and hyperuricemia is discussed.
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PMID:Nocturnal intragastric therapy in type I glycogen storage disease: effect on hormonal and amino acid metabolism. 28 65

Nine children with clinical diagnosis of glycogenoses were studied, types were confirmed through determination of levels and structure of glycogen, stimulation with glucagon and enzymatic defect analyses. Eight patients suffered glycogenoses type III and one, type VI. The major age group un type III was 1 to 2 years old (62.5%), the type VI was diagnosed in a preschool boy. Mean clinical features were: hepatomegaly, doll-like facies and short height. Major biochemical alterations were: transaminases elevation in both types, hypertriglyceridemia, hyperglycemia, metabolic acidosis and hyperuricemia only in glycogenoses III. One III type patient presented cardiovascular alterations. All patients showed increased concentrations of erythrocyte glycogen, with normal structure in type VI and abnormal in 75% of type III. Tree fourths of type III patients had a positive response to glucagon stimulation. No one presented glucose 6 phosphatase deficiency.
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PMID:[Hepatic glycogenosis: the clinical, biochemical and enzymatic aspects in a group of pediatric patients]. 134 Aug 24

The renal disease in an adult woman with Type 1 glycogen storage disease (GSD) is reported. Since she was 15 years old, several episodes of gouty arthritis had developed. At the age of 18, proteinuria was pointed out. Hepatomegaly, renomegaly out of proportion to the impairment of renal function, hyperuricemia, hyperlipidemia, fasting hypoglycemia and lactic acidemia were observed. The diagnosis of GSD was established on the basis of a glucose tolerance test, glucagon test and liver biopsy. The findings of renal biopsies performed at the ages of 24 and 27 years old suggested that glomerular damage might have preceded the tubulo-interstitial lesion.
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PMID:Renal disease in an adult with type 1 glycogen storage disease. 203 36

A 31-year-old male patient with type Ia glycogen storage disease was admitted to our department complaining of general fatigue and right hypochondriac pain. He exhibited massive hepatomegaly with systemic hypoglycemia, lactic acidosis, hyperuricemia, hyperpyruvatemia and hyperlipemia. The failure of blood glucose levels to increase after a glucagon loading test, and a reduced lactate level on glucose tolerance test were also observed. Various imaging techniques suggested hepatic adenoma with hemorrhage in the tumor, which was confirmed histologically. There was a complete absence of glucose 6-phosphatase activity, as determined by an enzyme assay on resected liver specimens, which proved the case to be type Ia glycogen storage disease. We also reviewed all previously reported cases of hepatic tumor and glycogen storage diseases. We conclude that, since hepatic adenoma is not rare in this disease, and is complicated by hemorrhage, rupture and malignancy, careful follow-ups are necessary.
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PMID:A case of type Ia glycogen storage disease complicated by hepatic adenoma. 217 Feb 59

Studies were performed to determine whether hypoglycemia or the glucagon response to hypoglycemia increases uric acid production in glycogen storage disease type I (glucose-6-phosphatase deficiency). Three adults with this disease had hyperuricemia (serum urate, 11.3-12.4 mg/dl) and reduced renal clearance of urate (renal urate clearance, 1.1-3.1 ml/min). These abnormalities were improved in one patient by intravenous glucose infusion for 1 mo, suggesting a role for hypoglycemia and its attendant effects on urate metabolism and excretion. A pharmacologic dose of glucagon caused a rise in serum urate from 11.4 to 13.0 mg/dl, a ninefold increase in urinary excretion of oxypurines, a 65% increase in urinary radioactivity derived from radioactively labeled adenine nucleotides, and a 90% increase in urinary uric acid excretion. These changes indicate that intravenous glucagon increases ATP breakdown to its degradation products and thereby stimulates uric acid production. To observe whether physiologic changes in serum glucagon modulate ATP degradation, uric acid production was compared during saline and somatostatin infusions. Serum urate, urinary oxypurine, radioactivity, and uric acid excretion increased during saline infusion as patients became hypoglycemic. Infusion of somatostatin suppressed these increases despite hypoglycemia and decreased the elevated plasma glucagon levels from a mean of 81.3 to 52.2 pg/ml. These data suggest that hypoglycemia can stimulate uric acid synthesis in glucose-6-phosphatase deficiency. Glucagon contributes to this response by activating ATP degradation to uric acid.
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PMID:Hyperuricemia in glycogen storage disease type I. Contributions by hypoglycemia and hyperglucagonemia to increased urate production. 285 25

The provision of small amounts of glucose during fasting is known to spare body protein and to attenuate markedly the metabolic response to starvation. These actions, which are not shared by fat, are generally thought to depend on the ability of exogenous glucose to stimulate insulin secretion. To determine whether fructose, a very weak insulin secretagogue, will also conserve nitrogen and alter the response to fasting, we infused small amounts of fructose, 100 g/d (375 kcal), into 7 obese subjects during a 10-day fast: 4 received fructose days 7 to 10, and 3 received fructose days 1 to 7. Fructose virtually abolished (all P less than 0.05-0.01) the fasting induced: (a) fall in glucose and insulin and rise in glucagon, (b) fall in triiodothyronine, (c) ketosis and acidosis, (d) increased ammonia excretion, (e) hyperuricemia (and hypouricosuria), and (f) fall in plasma alanine and rise in branched chain amino acids. Fructose also significantly reduced urinary sodium loss. Moreover, fructose exerted a prominent protein-sparing action, even though plasma insulin concentrations never exceeded postabsorptive levels. Excretion of total nitrogen was reduced by 40% to 50% during periods of fructose infusion, reflecting significant suppression of both urea and ammonia generation (all P less than 0.05-0.01). Most plasma glucogenic amino acids rose significantly during fructose administration. We conclude that low-dose fructose infusion essentially abolishes the entire hormone-substrate response to fasting, and spares body protein without raising insulin above postabsorptive levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitrogen conservation in starvation revisited: protein sparing with intravenous fructose. 351 Mar 63

A 29-year-old nullipara was admitted at 31 weeks' gestation because of toxemia. She noted gradually polyuria, severe thirst, malaise, nausea and anorexia. A water-deprivation test and administration of aqueous vasopressin confirmed the diagnosis of nephrogenic diabetes insipidus. At 33 weeks' gestation, blood chemistry studies revealed moderately elevated transaminase levels and hyperuricemia. Male twins were delivered by vacuum extraction at 35 weeks' gestation. After delivery, she became drousy and icterus appeared. Acute hepatic failure with marked hyperuricemia was diagnosed. She was treated with glucose solution with glucagon and soluble insulin, branched chain amino acids, gabexate mesilate, lactulose and famotidine. Her consciousness cleared rapidly and all laboratory data became normal by 15 days postpartum. The urine volume was about 5 liters per day from the first to sixth postpartum day. The diuresis decreased after the eighth postpartum day. Rare pregnancy complicated by transient nephrogenic diabetes insipidus and acute hepatic failure is discussed.
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PMID:Transient nephrogenic diabetes insipidus associated with acute hepatic failure in pregnancy. 365 42

Individuals with type Ia glycogen storage disease (glucose-6-phosphatase deficiency) frequently develop hepatic adenomas. Potential complications involving these adenomas include malignant transformation and hemorrhage. Five of 9 patients with this disease had evidence of hepatic filling defects on radionucleotide liver scan when first evaluated at our hospital. Dietary therapy aimed at preventing hypoglycemia was begun in 7 of the 9 patients. Prevention of hypoglycemia resulted in the correction of all of the metabolic abnormalities (lactic acidosis, hyperlipidemia, hyperuricemia, and growth retardation). Treatment also corrected the marked elevation in plasma glucagon concentrations. A disappearance of the hepatic lesions occurred in 2 of the treated patients, and a marked reduction in size of the adenoma occurred in the third patient. The hepatic filling defects remained present in the two untreated patients. None of the affected patients receiving dietary therapy have developed hepatic adenomas. One of these patients is now 22 yr old and has received dietary therapy for 7 yr. Early dietary therapy seems to be effective in preventing development of adenomas as well as inducing their resolution.
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PMID:Regression of hepatic adenomas in type Ia glycogen storage disease with dietary therapy. 694 8


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