AI Article Synopsis
- Insulin secretion from pancreatic β-cells relies on membrane potential and can be enhanced by blocking specific potassium channels, offering a safer alternative to KATP channel blockers for glucose-dependent insulin release.
- The study introduces a new insulin-stimulating compound derived from snake venom, called [Lys(52)]CTX-I(41-60), which is a modified version of the original cardiotoxin-I (CTX-I).
- Research indicates that this novel analogue likely activates Kv channels, making it a potential tool for studying β-cell function and a promising candidate for new type 2 diabetes treatments.
Article Abstract
Insulin secretion by pancreatic β-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 KATP 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-I(41-60) 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 Kv channels. This new analogue could represent a useful pharmacological tool to study β-cell physiology or even open a new therapeutic avenue for the treatment of type 2 diabetes.
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| http://dx.doi.org/10.1021/jm401904q | DOI Listing |
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