Nucleotide sensitivity of pancreatic ATP-sensitive potassium channels and type 2 diabetes.
Type 2 diabetes is generally perceived as a polygenic disorder, with disease development being influenced by both hereditary and environmental factors. However, despite intensive investigations, little progress has been made in identifying the genes that impart susceptibility to the common late-onset forms of the disease. E23K, a common single nucleotide polymorphism in K(IR)6.2, the pore-forming subunit of pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channels, significantly enhances the spontaneous open probability of these channels, and thus modulates sensitivities toward inhibitory and activatory adenine nucleotides. Based on previous association studies, we present evidence that with an estimated attributable proportion of 15% in Caucasians, E23K in K(IR)6.2 appears to be the most important genetic risk factor for type 2 diabetes yet identified.
Schwanstecher
Christina
C
Institute of Pharmacology and Toxicology, University of Braunschweig, Braunschweig, Germany. m.schwanstecher@tu-bs.de
Schwanstecher
Mathias
M
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009711:Nucleotides / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics
D009711:Nucleotides; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D000255:Adenosine Triphosphate