Nucleotide Sensitivity of Pancreatic ATP-Sensitive Potassium Channels and Type 2 Diabetes
- From the Institute of Pharmacology and Toxicology, University of Braunschweig, Braunschweig, Germany
Abstract
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 KIR6.2, the pore-forming subunit of pancreatic β-cell ATP-sensitive K+ (KATP) 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 KIR6.2 appears to be the most important genetic risk factor for type 2 diabetes yet identified.
Footnotes
-
Address correspondence and reprint requests to Dr. Mathias Schwanstecher, Institut für Pharmakologie und Toxikologie, Universität Braunschweig, Mendelssohnstraße 1, 38106 Braunschweig, Germany. E-mail: m.schwanstecher{at}tu-bs.de.
Received for publication 19 March 2002 and accepted in revised form 23 April 2002.
Emax, maximal effect; fK, frequency of the allele with K in position 23 of KIR6.2 in Caucasians; IC50, half-maximal inhibitory concentration value; KATP channel, ATP-sensitive potassium channel; KIR6.2, inwardly rectifying potassium channel subunit; OR, odds ratio; PHHI, persistent hyperinsulinemic hypoglycemia of infancy; PO, open probability; PPAR-γ, peroxisome proliferator-activated receptor-γ; SNP, single nucleotide polymorphism; SUR1, regulatory sulfonylurea receptor subunit 1; TCA, tricarboxylic acid.
The symposium and the publication of this article have been made possible by an unrestricted educational grant from Servier, Paris.
- DIABETES
