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)

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

Each of 12 types of glycogen storage disease (GSD O-XI) is delineated by clinical, biochemical and histologic features that allow its identification in future patients. GSD II occurs in 2 forms that are not both encountered in the same family. GSD IIa is the infantile fatal form with cardiomegaly, increased cardiac glycogen concentration and cardiac failure; GSD IIb is the adult form with clinically normal heart and normal cardiac glycogen concentration. Nonetheless, the heart muscle of both forms is equally deficient in acid alpha-glucosidase activity, and this raises questions as to the latter's role in the pathophysiology of GSD II. The appearance of hepatocytes in GSD IIa becomes normal after the administration of alpha-glucosidase. Using electron microscopy of uncultured amniotic fluid cells, the prenatal diagnosis of GSD IIa is feasible within one day after the amniocentesis. GSD VI and IX are instances of benign hepatomegaly except when GSD IX and III occur in the same child; one such patient died suddenly at home. There are 2 modes of inheritance in GSD IX: one (GSD IXa) is autosomal recessive, the other one (GSD IXb) is X-linked recessive. In either form the Km of the remaining liver phosphorylase kinase is normal. Both forms of GSD IX have the normal blood sugar response to glucagon, whereas GSD VI does not. Equally, the glucagon tolerance curve is flat in GSD XI although in vitro activity of glycolytic enzymes is normal. The in vivo administration of glucagon in GSD XI is followed by the normal increase of both urinary 3'5'-AMP and hepatic phosphorylase activity. GSD V may have increased activity of muscle phosphorylase kinase. Deficiencies of debrancher, liver phosphorylase and liver phosphorylase kinase can occur singly or in combination. Before any novel treatment of GSD is initiated, one should obtain tissue for the biochemical determination of the exact type of GSD. This is so because the clinical signs may not indicate the type with the necessary precision, and because some types are compatible with normal life and thus may not require therapy, especially if the latter is unproved and potentially dangerous.
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PMID:Glycogen storage diseases. 78 7

1. GSD-I is described in a child with partial deficiency of hepatic glucose-6-phosphatase. 2. Growth retardation and hepatosplenomegaly were major clinical features. 3. Hyperlipidaemia, lactic acidaemia, hyperuricaemia and reduced uric acid clearance were major biochemical findings. 4. Although the glucose response to glucagon and galactose was impaired, there was a striking absence of hypoglycaemia which may be attributable to residual catalytic activity of the enzyme. 5. Preliminary studies of the crude liver enzyme showed it to have a normal pH inactivation profile and apparent Km with a reduced Vmax. 6. No evidence of increased PP-ribose-P availability in fresh liver tissue was detected. 7. Continuous glucose feeding resulted in accelerated growth without complete correction of lactic acidosis or hyperuricaemia. 8. GSD-I with partial deficiency of hepatic glucose-6-phosphatase should be considered in patients with gout or hyperuricaemia associated with hypertriglyceridaemia and lactic acidaemia even in the absence of hypoglycaemia.
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PMID:Clinical and enzymological studies in a child with type I glycogen storage disease associated with partial deficiency of hepatic glucose-6-phosphatase. 615 47

A girl presented with an important growth retardation, hepatomegaly, fasting hypoglycemia, lactic acidosis, increased serum cholesterol, triglycerides and uric acid, and increased liver glycogen (7.5%). There was no rise in blood glucose after IV galactose or fructose, but glucagon gave a delayed response. Type Ib glycogen storage disease was suggested by the low normal activity of glucose-6-phosphatase (G-6-Pase) which reached 1.8 units/g (normal, 2 to 10 units/g) and the normal activity of other glycogenolytic enzymes, measured in homogenates prepared in H2O (mean +/- S.E. in control subjects: 59% +/- 7; in type Ia GSD: 92% +/- 3). The activity of G-6-Pase measured as described above increased to 3.8 units/g of liver 1 year after PCS and 7.85 units/g of liver after 3 years. At that time, a simultaneous assay of the enzyme in a fresh, previously not frozen liver biopsy, homogenized in 0.25 M sucrose, revealed only about 29% of the activity of the same sample prepared in H2O (mean +/- S.E. in three controls: 95.8% +/- 8.9.
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PMID:Clinical and biochemical findings before and after portacaval shunt in a girl with type Ib glycogen storage disease. 625 80

The plasma glucose, insulin, glucagon, lactate and amino acid response patterns to glucose and protein meals were examined in 11 patients with type III glycogen storage disease (GSD-III). The amino acid metabolism in GSD-III was shown to differ from that observed in normal subjects and in type I glycogen storage disease (GSD-I) patients. The outstanding findings involved the principal gluconeogenic amino acid, alanine. Postabsorptive levels of alanine in GSD-III were significantly below those of normal controls. Following glucose ingestion, alanine rose markedly in GSD-III, which differed from normal subjects in whom no change occurred, and from GSD-I patients in whom a sharp fall was observed. Following beef ingestion, the direction of change of alanine was similar in the three groups, but the circulating levels in GSD-III were significantly less than those observed in GSD-I and normal controls. The possibility that gluconeogenesis is enhanced in GSD-III was supported by the prompt rise in blood glucose observed following beef ingestion, which differed from GSD-I and normal subjects, in which no rise in glucose was observed.
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PMID:Amino acid disturbances in type III glycogenosis: differences from type I glycogenosis. 633 17

To determine whether patients with GSD-1 need nocturnal glucose therapy after completing physical growth and development, studies were performed on two consecutive nights. On the first night uncooked cornstarch (UCS) was given at the calculated glucose production rate at 21:00 h and 02:00 h. On the second night UCS was given at 21:00 h but omitted at 02:00 h. Six GSD-1 patients, aged 17.2-20.9 years, previously treated with continuous glucose therapy were studied. Measurements were made of plasma glucose (PG), serum insulin, growth hormone, cortisol, plasma glucagon (n = 4), and blood lactate at 30-60-min intervals. Serum uric acid, cholesterol, and triglycerides were measured at 21:00 h and 07:00 h, and serum FFA at 21:00 h, 02:00 h and 07:00 h on the first night and immediately before treatment for hypoglycaemia on the second night. For five hours after UCS at 21:00 h, mean PG, serum insulin and blood lactate concentrations were similar on the two nights. With UCS at 02:00 h, mean PG concentrations were > or = 4.1 mmol/L from 02:00 to 07:00 h. Without UCS at 02:00 h, in all subjects PG concentrations fell to < 2.5 mmol/L after 6.5-8.5 h and mean blood lactate concentration increased to 7.4 +/- 3.0 mmol/L. Young adults with GSD-1 developed hypoglycaemia and hyperlactataemia after a relatively brief period without exogenous glucose and, therefore, need to continue nocturnal glucose therapy to prevent fasting hypoglycaemia.
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PMID:Biochemical evidence for the requirement of continuous glucose therapy in young adults with type 1 glycogen storage disease. 796 79

There are 3 cases of liver type glycogen storage diseases. All of them presented with protruding abdomen, failure to thrive, doll face and mark hepatomegaly. Laboratory findings were hypoglycemia, metabolic acidosis, abnormal liver function test, hyperlipidemia and prolonged bleeding time in GSD Ia. GSD III has no hypoglycemia and borderline hyperuricemia. Glucagon stimulation test helps to differentiate typing. The aim of treatment is to prevent hypoglycemia, suppress lactic acid production, decrease blood lipid and uric acid levels and enhances statural growth by uncooked cornstarch. Complications such as epistaxis and suspected liver adenoma have to be closely followed up. Genetic counseling for both types GSD are autosomal recessive with recurrence risk of 25%. Prenatal diagnosis by enzymes assay or molecular diagnosi are not available in this hospital.
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PMID:Glycogen storage diseases in Thai patients: Phramongkutklao Hospital experience. 1685 72

Glycogen storage disease type III (GSD-III) is an autosomal recessive disorder caused by the lack of amylo-1,6-glucosidase (AGL), one of the catalytic domains of the glycogen debranching enzyme. Deficiency of this enzyme classically results in hepatomegaly and ketotic hypoglycemia. The diagnosis of the disorder was previously confirmed with a liver biopsy demonstrating abnormal liver glycogen content and absent enzyme activity. We describe an 11 month-old African-American Jehovah's Witness male with non-ketotic hypoglycemia (NKH), hepatomegaly, cardiomyopathy, and a flat glucagon response confirmed to have GSD-IIIa by mutation analysis of the AGL gene. The present case represents an unusual presentation (NKH) of GSD-IIIa and emphasizes the utility of the newly approved commercially available Clinical Laboratory Improvement Advisory Committee (CLIA) mutation analysis test.
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PMID:Glycogen storage disease type IIIa presenting as non-ketotic hypoglycemia: use of a newly approved commercially available mutation analysis to non-invasively confirm the diagnosis. 1871 45