PubMed 19103161

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv2.1 , Kv2.2

Title: SNAP-25(1-180) enhances insulin secretion by blocking Kv2.1 channels in rat pancreatic islet beta-cells.

Authors: Guo-qing Zhuang, Wei Wu, Fen Liu, Jun-li Ma, Yan-xia Luo, Zhong-xin Xiao, Yan Liu, Wei Wang, Yan He

Journal, date & volume: Biochem. Biophys. Res. Commun., 2009 Feb 20 , 379, 812-6

PubMed link:

Voltage-gated outward K(+) currents from pancreatic islet beta-cells are known to repolarize the action potential during a glucose stimulus, and consequently to modulate Ca(2+) entry and insulin secretion. The voltage gated K(+) (Kv) channel, Kv2.1, which is expressed in rat islet beta-cells, mediates over 60% of the Kv outward K(+) currents. A novel peptidyl inhibitor of Kv2.1/Kv2.2 channels, guangxitoxin (GxTX)-1, has been shown to enhance glucose-stimulated insulin secretion. Here, we show that SNAP-25(1-180) (S180), an N-terminal SNAP-25 domain, but not SNAP-25(1-206) (S206), inhibits Kv current and enhances glucose-dependent insulin secretion from rat pancreatic islet beta-cells, and furthermore, this enhancement was induced by the blockade of the Kv2.1 current. This study indicates that the Kv2.1 channel is a potential target for novel therapeutic agent design for the treatment of type 2 diabetes. This target may possess advantages over currently-used therapies, which modulate insulin secretion in a glucose-independent manner.