Journal
HUMAN MUTATION
Volume 30, Issue 2, Pages 170-180Publisher
WILEY
DOI: 10.1002/humu.20838
Keywords
permanent neonatal diabetes; transient neonatal diabetes; hyperinsulinemia of infancy; potassium channel; sulfonylurea receptor; inwardly rectifying; KCNJ11; Kir6.2; ABCC8; SUR1
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Funding
- Wellcome Trust
- Sir Graham Wilkins Studentship
- Research Councils UK (RCUK) research fellow
- Diabetes UK R.D. Lawrence research fellow
- Medical Research Council [G0700222] Funding Source: researchfish
- MRC [G0700222] Funding Source: UKRI
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The beta-cell ATP-sensitive potassium (K-ATP) channel is a key component of stimulus-secretion coupling in the pancreatic beta cell. The channel couples metabolism to membrane electrical events bringing about insulin secretion. Given the critical role of this channel in glucose homeostasis it is therefore not surprising that mutations in the genes encoding for the two essential subunits of the channel can result in both hypo- and hyperglycemia. The channel consists of four subunits of the inwardly rectifying potassium channel Kir6.2 and four subunits of the sulfonylurea receptor 1 (SUR1) : It has been known for some time that loss of function mutations in KCNJ11, which encodes for Kir6.2, and ABCC8, which encodes for SUR1, can cause over-secretion of insulin and result in hyperinsulinism of infancy, while activating mutations in KCNJ11 and ABCC8 have recently been described that result in the opposite phenotype of diabetes. This review focuses on reported mutations in both genes, the spectrum of phenotypes, and the implications for treatment on diagnosing patients with mutations in these genes.
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