The Common Single Nucleotide Polymorphism E23K in KIR6.2 Sensitizes Pancreatic β-Cell ATP-Sensitive Potassium Channels Toward Activation Through Nucleoside Diphosphates

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. suppl 3; pp. S363 - S367
• Main Authors: Schwanstecher, Christina, Neugebauer, Bettina, Schulz, Miriam, Schwanstecher, Mathias
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01.12.2002
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.2007.S363

E23K, a common polymorphism in the pore-forming subunit KIR6.2 of pancreatic β-cell ATP-sensitive K+ (KATP) channels, is functionally relevant and thus might play a major role in the pathophysiology of common type 2 diabetes. In this study, we show that in the simultaneous presence of activatory and inhibitory nucleotides, the polymorphism exerts opposite effects on the potencies of these modulators: channel opening through nucleoside diphosphates is facilitated, whereas sensitivity toward inhibition through ATP is slightly decreased. The results support the conclusion that E23K predisposes to type 2 diabetes by changing the channel’s response to physiological variation of cytosolic nucleotides, resulting in KATP overactivity and discrete inhibition of insulin release.