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Updated: May 2, 2026

An In Ovo Model for Testing Insulin-mimetic Compounds
Published on: April 23, 2018
Design of a truncated cardiotoxin-I analogue with potent insulinotropic activity
Thi Tuyet Nhung Nguyen1, Benjamin Folch, Myriam Létourneau
1INRS-Institut Armand-Frappier , Université du Québec , 531 Boulevard des Prairies Ville de Laval, Québec H7 V 1B7, Québec Canada.
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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