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Mutations in the genes encoding the pancreatic beta‐cell K ATP channel subunits Kir6.2 ( KCNJ11 ) and SUR1 ( ABCC8 ) in diabetes mellitus and hyperinsulinism
Author(s) -
Gloyn Anna L.,
Siddiqui Juveria,
Ellard Sian
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20292
Subject(s) - biology , kir6.2 , congenital hyperinsulinism , hyperinsulinism , genetics , beta cell , gene , mutation , sulfonylurea receptor , diabetes mellitus , protein subunit , endocrinology , insulin resistance , islet
The beta‐cell ATP‐sensitive potassium 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 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. 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 oversecretion of insulin and result in hyperinsulinemia (HI) of infancy; however, heterozygous activating mutations in KCNJ11 that result in the opposite phenotype of diabetes have recently been described. This review focuses on reported mutations in both genes, the spectrum of phenotypes, and the implications for treatment when patients are diagnosed with mutations in these genes. Hum Mutat 27(3), 220–231, 2006. © 2006 Wiley‐Liss, Inc.