Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel.

Journal article

OBJECTIVE: In the pancreatic beta-cell, ATP-sensitive K(+) (K(ATP)) channels couple metabolism with excitability and consist of Kir6.2 and SUR1 subunits encoded by KCNJ11 and ABCC8, respectively. Sulfonylureas, which inhibit the K(ATP) channel, are used to treat type 2 diabetes. Rare activating mutations cause neonatal diabetes, whereas the common variants, E23K in KCNJ11 and S1369A in ABCC8, are in strong linkage disequilibrium, constituting a haplotype that predisposes to type 2 diabetes. ...

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Authors: Hamming, K; Soliman, D; Matemisz, L; Niazi, O; Lang, Y

• Journal: Diabetes
• Volume: 58
• Issue: 10
• Pages: 2419-2424
• Publication date: 2009-10-01
• DOI: 10.2337/db09-0143
• EISSN: 1939-327X
• ISSN: 0012-1797
• Language: English
• Keywords: Genetic Variation; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; KATP Channels; Diabetes Mellitus, Type 2; Potassium Channels, Inwardly Rectifying; Sulfonylurea Compounds; ATP-Binding Cassette Transporters; Adenosine Triphosphate; Homozygote; Receptors, Drug; Amino Acid Substitution