Defective ABCC8 does not form functional KATP channels, causing hyperinsulinemic hypoglycemia

Stable Identifier
R-HSA-5683113
Type
Reaction [transition]
Species
Homo sapiens
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ATP-binding cassette sub-family C member 8 (ABCC8) is a subunit of the beta-cell ATP-sensitive potassium channel (KATP). KATP channels play an important role in the control of insulin release. Elevation of the ATP:ADP ratio closes KATP channels leading to cellular depolarisation, calcium influx and exocytosis of insulin from its storage granules. Defects in ABCC8 can cause dysregulation of insulin secretion resulting in hyperglycemias or hypoglycemias.

Familial hyperinsulinemic hypoglycemia (see HHF1; MIM:256450) is a disorder caused by defective negative feedback regulation of insulin secretion (persistent hyperinsulinism) leading to severe hypoglycemia. The most commom ABCC8 mutations causing HHF1 include F1388del, A1330Gfs*35, V187D and E1507K (Thomas et al. 1995, Nestorowicz et al. 1996, Otonkoshi et al. 1999).

Literature References
PubMed ID Title Journal Year
7847376 Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy

Thomas, PM, Cote, GJ, Hallman, DM, Mathew, PM

Am. J. Hum. Genet. 1995
8923011 Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews

Nestorowicz, A, Wilson, BA, Schoor, KP, Inoue, H, Glaser, B, Landau, H, Stanley, CA, Thornton, PS, Clement, JP, Bryan, J, Aguilar-Bryan, L, Permutt, MA

Hum. Mol. Genet. 1996
10334322 A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland

Otonkoski, T, Ammälä, C, Huopio, H, Cote, GJ, Chapman, J, Cosgrove, K, Ashfield, R, Huang, E, Komulainen, J, Ashcroft, FM, Dunne, MJ, Kere, J, Thomas, PM

Diabetes 1999
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
hyperinsulinemic hypoglycemia 13317 Islet cell hyperplasia, nesidioblastosis, persistent hyperinsulinemia hypoglycemia of infancy
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