Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 379, Issue 4, Pages 812-816Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.12.059
Keywords
Voltage-gated potassium (K-v) channel; SNAP-25; Glucose-dependent; Insulin
Categories
Funding
- National Natural Science Foundation of China [30670778]
- Beijing Municipal Science & Technology Nova Plan [2007A075]
- Beijing Municipal Special Fund for Outstanding Personnel Training [20061D0501800254]
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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 Ca2+ 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. (C) 2008 Published by Elsevier Inc.
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