GDH-HI (hyperinsulinism hyperammonemia syndrome; HI/HA syndrome) caused by GLUD1
-activating mutations is the second most common cause of congenital hyperinsulinism (CHI MIM256450), which is a genetic and phenotypic heterogeneous group of disorders associated with dysregulated insulin secretion .
Until recently mutations in only 12 different genes (ABCC8, KCNJ11, GLUD1
, GCK, HADH, SLC16A1, HNF4A, HNF1A, HK1, PGM1 and PMM2) that lead to dysregulated secretion of insulin had been described (6,13,14,15,16,17,18).
Mutations in the glucokinase (GCK), glutamate dehydrogenase (GLUD1
), insulin receptor (INSR), hepatocyte nuclear factor 4a (HNF4A), and monocarboxylate transporter 1 (SLC16A1) genes have less commonly been reported to cause CHI and similar syndromes featuring hyperinsulinemic hypoglycemia [4-8].
In addition to the normal mammalian glutamate dehydrogenase gene, GLUD1
, primates have a second glutamate dehydrogenase gene, GLUD2, that is expressed in astrocytes and may be needed in those cells to preserve alpha-ketoglutarate levels in the presence of high glutamine synthetase activity .
Lawrence, "Catalogue of alleles for the complex gene loci GluA1, GluB1, GluD1
, which code for the highmolecular-weight subunits of glutenin in hexaploid wheat," Cereal Research Communications, vol.
 Human genes: ABCC8, ATP-binding cassette subfamily C, member 8; KCNJ11, potassium inwardly rectifying channel, subfamily J, member 11; GCK, glucokinase; GLUD1
, glutamate dehydrogenase 1; HADH, hydroxyacyl-Coenzyme A dehydrogenase; SLC16A1, solute carrier family 16, member 1 (monocarboxylic acid transporter 1).
1RL.1DL.1RL) was combined with a translocation of the GluD1
locus to chromosome 1A of triticale, in a germplasm UCRTCL3-2001.
Excessive ROS production mediated by the necrosome occurs through the following mechanisms: (a) RIP3 can allosterically activate glutamate-ammonia ligase or glutamine synthetase (GLUL) and glutamate dehydrogenase (GLUD1
Mutations in 11 genes, including ABCC8, KCNJ11, GLUD1
, GCK, HADH, UCP2, SLC16A1 (MCT1), HNF4A, HNF1A (6), HK1 (7), and PGM1 (8) are known to cause CHI.
The senescent MVs contained a new protein, G6PD, and showed a higher PS for PGD and GLUD1
was the most abundant protein in MVs of both ages.
Persistent CHI can be caused by mutations in nine genes regulating the insulin secretion from the ([beta]-cells (ABCC8, KCNJ11, GLUD1
, HADH, GCK, HNF4A, HNF1A, SLC16A1, and UCP2 genes) (6,7).
The former are attributed to adenosine triphosphate (KATP)-sensitive potassium channel genes (ABCC8, KCNJ11) and metabolopathies regulate different pathways (GLUD1
, GCK, HNF4A, HNF1A, SLC16A1, UCP2, HADH).