Cardiotoxin-I: an unexpectedly potent insulinotropic agent.
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.
INRS-Institut Armand-Frappier, Université du Québec, 531 Boulevard des Prairies, Ville de Laval, Québec H7V 1B7, Canada.
Thi Tuyet Nhung
TT
Nguyen
Benjamin
B
Folch
Myriam
M
Létourneau
David
D
Vaudry
Nam Hai
NH
Truong
Nicolas
N
Doucet
David
D
Chatenet
Alain
A
Fournier
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival; D005591:Chemical Fractionation; D004179:Cobra Cardiotoxin Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045424:Complex Mixtures / Q000737:chemistry; D004546:Elapid Venoms / Q000737:chemistry*; D017815:Elapidae / Q000502:physiology; D004912:Erythrocytes / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051381:Rats; D046509:Tissue Culture Techniques
D004179:Cobra Cardiotoxin Proteins; D045424:Complex Mixtures; D004546:Elapid Venoms; D007004:Hypoglycemic Agents; D007328:Insulin; C521753:Naja kaouthia venom; D007770:L-Lactate Dehydrogenase; D005947:Glucose