The common single nucleotide polymorphism E23K in K(IR)6.2 sensitizes pancreatic beta-cell ATP-sensitive potassium channels toward activation through nucleoside diphosphates.
Diabetes
; 51 Suppl 3: S363-7, 2002 Dec.
Article
en En
| MEDLINE
| ID: mdl-12475776
ABSTRACT
E23K, a common polymorphism in the pore-forming subunit K(IR)6.2 of pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) 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 K(ATP) overactivity and discrete inhibition of insulin release.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Canales de Potasio
/
Adenosina Trifosfato
/
Islotes Pancreáticos
/
Polimorfismo de Nucleótido Simple
/
Canales de Potasio de Rectificación Interna
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Diabetes
Año:
2002
Tipo del documento:
Article
País de afiliación:
Alemania