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)

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

A 5-year-old Black boy presented with massive hepatomegaly and muscle weakness. Liver biopsy revealed the presence of glycogen pools in the cytoplasm and nuclei of hepatocytes. Erythrocyte glycogen levels, identified as limit dextrin, were grossly increased. The galactose tolerance test as well as the two-stage glucagon stimulation test suggested a decrease in activity of both amylo-1,6-glucosidase and glucose-6-phosphatase enzymes. This was confirmed by direct assays performed on liver tissue and erythrocytes. The decrease in glucose-6-phosphatase activity was attributed to a secondary effect of limit dextrin.
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PMID:Glycogen storage disease type III. A case report. 632 Apr 74

Previous studies have suggested that reduction of dietary fat intake, with or without caloric restriction, may lead to improvement in certain of the characteristic abnormalities that accompany total lipodystrophy (TLD). We have studied the effects of eucaloric medium chain triglyceride (MCT) substitution for dietary long chain fatty acids in a patient with acquired total lipodystrophy and unusual somatic and visceral anomalies. The patient exhibited insulin resistance, carbohydrate intolerance, striking fasting- and glucose-stimulated hyperinsulinemia, hyperglucagonemia, type V hyperlipoproteinemia, and lipoprotein lipase deficiency on a normal diet. Improvement in chylomicronemia, hypertriglyceridemia, and xanthomatosis occurred during eucaloric MCT substitution. Carbohydrate intolerance decreased and fasting immunoreactive glucagon and insulin concentrations fell 37% and 83%, respectively. Plasma triglyceride polyunsaturated fatty acid concentrations decreased to very low levels. With long term MCT feeding supplemented by polyunsaturated fatty acids, hepatomegaly has gradually decreased, while body weight has remained stable. The patient has not yet required insulin therapy. These observations suggest that the abnormalities in carbohydrate metabolism are closely linked to, and perhaps dependent on, the abnormalities in lipoprotein transport in TLD. Long chain triglyceride restriction and MCT supplementation should be attempted in additional patients with the features of TLD to determine whether this is a generally effective therapeutic approach.
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PMID:Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids in acquired total lipodystrophy: effects on hyperlipoproteinemia and endogenous insulin resistance. 634 62

Rats from an inbred strain (NZR/Mh) were found to have high concentrations of glycogen in their livers, even after 24 h of starvation. Despite this, blood glucose concentrations were well maintained on starvation for up to 72 h. The primary defect is a deficiency of liver phosphorylase kinase, causing a lack of active glycogen phosphorylase, although total phosphorylase is normal. The intravenous injection of glucagon caused a rapid activation of cyclic AMP-dependent protein kinase in the liver, but no increase in either phosphorylase kinase or phosphorylase a activity. Although total glycogen synthase activity in the livers of affected rats was higher than normal, glycogen synthase in the active form was very low, presumably as a result of the high liver glycogen content. The condition is transmitted as autosomal recessive and, apart from hepatomegaly, the affected rats appear healthy.
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PMID:Glycogen-storage disease in rats, a genetically determined deficiency of liver phosphorylase kinase. 693 96

The features of 41 proven or suspected cases of pancreatic glucagonoma and one possible case of renal glucagonoma have been reviewed. Glucagonoma is one form of islet cell neoplasm and involves pancreatic alpha cells. It may occur more frequently in women and is more likely to be malignant than insulinoma. Patients may present with glucose intolerance, an erythematous, eczematous dermatitis, glossitis, stomatitis, vaginitis and unexplained weight loss. Anemia, hypoproteinemia, hypoaminoacidemia and hypolipidemia may also be present. Malignant glucagonoma metastasizes frequently to liver. An evaluation for possible glucagonoma may be considered in a patient with the characteristic eczematous dermatitis, glossitis or stomatitis and glucose intolerance, an unusual or atypical history of diabetes mellitus, or hepatomegaly with other characteristics of glucagonoma. Initial evaluation may include measurement of fasting plasma glucagon concentration, and an oral glucose tolerance test with measurements of plasma glucose and glucagon levels. Extreme fasting hyperglucagonemia, and a paradoxical rise in plasma glucagon concentrations after glucose ingestion should strongly suggest the presence of glucagonoma. Radiographic demonstration of pancreatic glucagonoma is best carried out by celiac arteriography. Surgical excision of the tumor is the treatment of choice. Nonresectable lesions may respond to chemotherapy with streptozotocin. Treatment for the various dermatologic or metabolic complications of glucagonoma which include glucose intolerance, hypoproteinemia, hypocholesterolemia and anemia may not be satisfactory. Glucose intolerance is usually mild and may be adequately treated with dietary or insulin therapy. Rarely, glucagonoma with massive destruction of the pancreas or other factors may induce severe glucose intolerance. In contrast, the anemia, skin rash, and hypoproteinemia do not respond to conservative therapies tested thus far. Glucagonoma is a model for studying the importance of glucagon in causing the hyperglycemia of diabetes mellitus. Study of patients with glucagonoma does suggest that glucagon has some role in the etiology of hyperglycemia in diabetic states; however, as in studies on diabetes, investigations on glucagonoma do not demonstrate that glucagon has a primary role in producing severe glucose intolerance.
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PMID:Clinical and metabolic aspects of glucagonoma. 698 81

Various metabolic studies were performed in a patient with the idiopathic Fanconi syndrome in whom constant ketonuria suggested that organic acidemia might contribute to the metabolic acidosis. Glucose intolerance with a diminished insulin release was found after PO or IV glucose loads and after glucagon administratio. An insulinopenic "diabetes-like" state has not previously been described in such patients. The patient had impaired galactose-glucose interconversion, elevated blood lactate levels, reduced pyruvate levels, and an increased lactate:pyruvate ratio. Hepatomegaly and hypoglycemia were not present, and liver and muscle biopsies revealed no enzymatic evidence of glycogenosis. The erythrocyte UDP galactose transferase activity was normal. The patient failed to convert fructose to glucose and had a rise in blood lactate after ethanol administration. Further studies revealed no production of glucose after alanine or glycerol administraion, each test being associated with elevated blood lactate levels and, after alanine, an increased lactate:pyruvate ratio. The lactate:pyruvate ratio was elevated after glucagon administration with increased lactate and reduced pyruvate concentrations.
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PMID:Abnormalities of carbohydrate metabolism in idiopathic Fanconi syndrome. 738 41

A male child presented at 5 months of age with vomiting, diarrhoea, hypoglycaemia and hepatomegaly. Histology on a frozen liver biopsy suggested glycogen storage disease (GSD), while biochemical analyses confirmed an elevated glycogen content and normal activities of the GSD enzymes with the proviso that a variant of GSD 1 should be considered. The patient presented at 9 months of age with severe lactic acidosis and hypoglycaemia. A glucagon tolerance test and galactose load test on the patient produced no glycaemic response. A second biopsy was obtained and appropriately handled for the investigation of variants of the glucose-6-phosphatase enzyme (G6Pase) complex. Results showed that the patient had a deficiency of two transport proteins of the G6Pase complex, namely glucose-6-phosphate translocase and pyrophosphate translocase, i.e. GSD 1b/1c beta. These results were confirmed by additional kinetic analyses which provided confirmation of the double translocase deficiency. Evidence for inhibitors to these translocases was not found. The patient's treatment has resulted in the hypoglycaemia now being well controlled; however, at 3 years of age, height and weight are markedly lagging and he is moderately developmentally delayed. Neutropenia has not been found and neutrophil function is normal. Double enzyme deficiencies are very rare and possible explanations which might lead to this phenotype are considered. This, to the authors' knowledge, is the first report of a double translocase deficiency causing GSD type 1.
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PMID:Multiple transport protein defects in a patient with glycogen storage disease type 1: GSD 1b/1c beta. 859 36

We studied 20 children with a clinical picture and laboratory study suggestive of hepatic glycogenosis. The age of the beginning of symptoms varied from birth to 24 months and the age at the diagnosis varied from 2 to 81 months. Hepatomegaly was found in all patients, diarrhea in 65% (13/26), "doll-face" in 55% (11/20) and convulsions in 50% (10/20). Nutritional evaluation showed more height deficiency than weight deficiency. Laboratory tests showed elevation of hepatic transaminases (12/19), hypercolesterolemia (8/14), hyperuricemia (6/17) and hypoglycemia (6/20). Liver function was not compromised in most of the cases. The results of glucagon tolerance test were variable. The histoenzymology study performed in 15 patients revealed the following results: Type VI (liver phosphorylase deficiency) in seven, Type I (glucose-6-phosphatase deficiency) in two, Type IV (brancher enzyme) in one and no conclusion could be drawn in five patients. The finding of hypoglycemia in few cases of this study can be justified by the few number of glycogenosis Type I, probably due to the fact that this type is the most easily diagnosed, with less necessity of referring them to specialized centers.
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PMID:[Hepatic glycogenosis in childhood: clinical and laboratory findings in 20 patients]. 872 90

A rare case of severe acute hepatitis A complicated by pure red cell aplasia (PRCA) is reported. A 60-year-old man with jaundice and hepatomegaly was diagnosed as having acute hepatitis A by positive IgM anti-hepatitis A antibody (anti-HAV). Severe anemia rapidly developed 3 weeks after admission, and the patient was diagnosed with PRCA by both bone marrow smears and erythrocyte survival study. The anemia was transient and bone marrow recovered within 1 week. However, concomitant with bone marrow recovery, the hepatitis worsened. He became drowsy and disoriented and severe jaundice, ascites, prolonged prothrombin time, increased transaminase levels, and abnormal electroencephalogram (EEG) were exhibited. Plasma exchange transfusion and glucagon-insulin (GI) therapy improved the consciousness level, but bilirubin, transaminase levels, and IgM anti-HAV titer remained high. Intravenous administration of lipophilized prostaglandin E1 (lipo-PGE1) was added to the GI therapy. Bilirubin and transaminase levels were normalized in the 8th week after the initiation of this combination therapy (17 weeks after admission). The combined use of lipo-PGE1 with plasma exchange and GI therapy appeared to be useful for the prolonged severe hepatitis in this patient.
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PMID:Severe acute hepatitis A associated with acute pure red cell aplasia. 884 89

Phosphorylase kinase-deficient liver glycogenosis manifests in infancy with hepatomegaly, growth retardation, and elevated plasma aminotransferases and lipids. It can be caused by mutations in three different genes of phosphorylase kinase subunits: PHKA2, PHKB, and PHKG2. It is usually a benign condition, often with complete resolution of symptoms during puberty. A minority of patients displays a more severe phenotype with symptomatic fasting hypoglycemia and abnormal liver histology that may progress to cirrhosis. Three patients with liver cirrhosis in childhood analyzed previously all had PHKG2 mutations. This suggested that this genotype may generally cause a more severe clinical manifestation, but to date PHKG2 mutations have been identified in only seven patients. Here, we report mutation analysis in three new patients with liver phosphorylase kinase deficiency and recurrent hypoglycemia, liver fibrosis, and lack of glucagon response but no overt cirrhosis. In all three patients, PHKG2 mutations were found (H89fs[insC], E157K, D215N, W300X). Three of these mutations are novel, bringing the total number of distinct human PHKG2 mutations to 11, found in 10 patients. We conclude that liver phosphorylase kinase deficiency with a severe phenotype, with or without cirrhosis, is indeed often caused by PHKG2 mutations. These patients require active measures to maintain normoglycemia (raw cornstarch, nocturnal tube feeding), which may also alleviate growth retardation and the development of abnormal liver histology.
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PMID:Severe phenotype of phosphorylase kinase-deficient liver glycogenosis with mutations in the PHKG2 gene. 1293 Sep 17


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