Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperinsulinism in infancy (HI) is a condition of neonates and early childhood. For many years the pathophysiology of this potentially lethal disorder was unknown. Advances in the genetics, histopathology and molecular physiology of this disease have now provided insights into the causes of beta-cell dysfunction and revealed levels of diversity far in excess of our previous knowledge. These include defects in ion channel subunit genes and mutations in several enzymes associated with beta-cell metabolism and anaplerosis. In most cases, beta-cell pathophysiology leads to an alteration in the function of ATP-sensitive K(+) channels. This can manifest as 'channelopathies' of K(ATP) channels through gene defects in ABCC8 and KCNJ11 (Ch.11p15); or as a result of 'metabolopathies' through defects in the genes encoding glucokinase (GCK, Ch.7p15-p13), glutamate dehydrogenase (GLUD1, Ch.10q23.3) and short-chain L-3-hydroxyacyl-CoA dehydrogenase (HADHSC, Ch.4q22-q26). This review focuses upon the relationship between the causes of HI and therapeutic options.
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PMID:Genetics and pathophysiology of hyperinsulinism in infancy. 1498 44

Congenital hyperinsulinism is characterized by the unregulated secretion of insulin from pancreatic Beta-cells. The inappropriate insulin secretion causes severe and persistent hypoglycaemia, which is a potent cause of brain damage if inappropriately managed. So far mutations in 5 different genes have been described which lead to inappropriate insulin secretion. The most common cause of congenital hyperinsulinism is autosomal recessive mutations in the genes ABCC8 and KCNJ11 encoding the 2 subunits (SUR 1 and Kir6.2, respectively) of the pancreatic Beta-cell ATP-sensitive potassium channel. Autosomal dominant mutations in the genes encoding glucokinase (GCK) and glutamate dehydrogenase (GLUD1) lead to inappropriate insulin secretion by increasing the ATP/ADP ratio in the Beta-cells. Autosomal recessive mutations in the HADHSC gene (encoding the enzyme short-chain L-3-hydroxyacyl-CoA dehydrogenase) have been linked to defects in fatty acid oxidation and hyperinsulinism. Finally some patients have been described with exerciseinduced hyperinsulinaemic hypoglycaemia but the genetic basis of this is unclear at present. Recent advances in 18fluoro-L-Dopa positron emission tomography scanning suggest that this is a highly sensitive method for differentiating diffuse from focal disease as well as accurately locating the focal lesion. Despite huge advances in the last 10 years the mechanisms leading to hyperinsulinaemic hypoglycaemia are still unknown in >50% of patients.
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PMID:Insights in congenital hyperinsulinism. 1798 31