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Abstract: Voltage-gated outward K+ currents from pancreatic islet β-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 β-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-251–180 (S180), an N-terminal SNAP-25 domain, but not SNAP-251–206 (S206), inhibits Kv current and enhances glucose-dependent insulin secretion from rat pancreatic islet β-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. [Copyright &y& Elsevier]

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.

Purpose: To explore the needs for basic community-based rehabilitation services for disabled persons in Xuanwu District, Beijing, China, and to identify factors which influence disabled persons to accept rehabilitation services., Method: One hundred and eight disabled persons were selected by systematic sampling and simple random sampling to assess their needs for community-based rehabilitation services., Results: Of the interviewees, 57.4% needed the community-based rehabilitation services, but only 13.9% took advantage of it. The main factors influencing the interviewees to accept these services were cost (P < 0.05), knowledge about rehabilitation medicine (P < 0.05); and the belief in the therapeutic benefit of the community-based rehabilitation service (P < 0.05)., Conclusion: A considerable gap exists between the supply of community-based rehabilitation services in Beijing and the needs for these services by disabled residents underscoring the need for improved availability, and for additional research.