科研之友
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摘要
Insulin secretion by pancreatic beta-cells in response to glucose or other secretagogues is tightly coupled to membrane potential. Various studies have highlighted the prospect of enhancing insulin secretion in a glucose-dependent manner by blocking voltage-gated potassium channels (K-v) and calcium-activated potassium channels (K-Ca). Such strategy is expected to present a lower risk for hypoglycemic events compared to K-ATP channel blockers. Our group recently reported the discovery of a new insulinotropic agent, cardiotoxin-I (CTX-I), from the Naja kaouthia snake venom. In the present study, we report the design and synthesis of [Lys(52)]CTX-I41-60 via structure-guided modification, a truncated, equipotent analogue of CTX-I, and demonstrate, using various pharmacological inhibitors, that this derivative probably exerts its action through K-v channels. This new analogue could represent a useful pharmacological tool to study beta-cell physiology or even open a new therapeutic avenue for the treatment of type 2 diabetes.
- 出版日期2014-3-27
