Cardiotoxin-I: An Unexpectedly Potent Insulinotropic Agent

• Published in: Chembiochem : a European journal of chemical biology 2012-08, Vol.13 (12), p.1805-1812
• Main Authors: Nguyen, Thi Tuyet Nhung, Folch, Benjamin, Létourneau, Myriam, Vaudry, David, Truong, Nam Hai, Doucet, Nicolas, Chatenet, David, Fournier, Alain
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Aorta - drug effects; Biochemistry, Molecular Biology; cardiotoxin-I; Cell Line; Cell Survival; Chemical Fractionation; Cobra Cardiotoxin Proteins - chemistry; Cobra Cardiotoxin Proteins - isolation & purification; Cobra Cardiotoxin Proteins - pharmacology; Complex Mixtures - chemistry; Elapid Venoms - chemistry; Elapidae - physiology; Erythrocytes - drug effects; Glucose - metabolism; Glucose - pharmacology; Hemolysis - drug effects; Humans; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - isolation & purification; Hypoglycemic Agents - pharmacology; insulin; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; ion channels; L-Lactate Dehydrogenase; Life Sciences; Models, Molecular; Molecular Sequence Data; peptides; Rats; Structural Biology; structure-function relationships; Tissue Culture Techniques
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201200081

Insulin secretion from pancreatic β‐cells is a complex process, involving the integration and interaction of multiple external and internal stimuli, in which glucose plays a major role. Understanding the physiology leading to insulin release is a crucial step toward the identification of new targets. In this study, we evaluated the presence of insulinotropic metabolites in Naja kaouthia snake venom. Only one fraction, identified as cardiotoxin‐I (CTX‐I) was able to induce insulin secretion from INS‐1E cells without affecting cell viability and integrity, as assessed by MTT and LDH assays. Interestingly, CTX‐I was also able to stimulate insulin secretion from INS‐1E cells even in the absence of glucose. Although cardiotoxins have been characterized as potent hemolytic agents and vasoconstrictors, CTX‐I was unable to induce direct hemolysis of human erythrocytes or to induce potent vasoconstriction. As such, this newly identified insulin‐releasing toxin will surely enrich the pool of existing tools to study β‐cell physiology or even open a new therapeutic avenue. Virtues of venom: Cardiotoxin‐I, isolated from Naja kaouthia snake venom, is able to produce concentration‐dependent insulin release from INS‐1E cells both in the presence and absence of glucose. Further evaluation showed that this toxin does not have hemolytic or cytotoxic characteristics, thus suggesting its potential as a tool to study insulin secretion or as a new therapeutic agent.