Toxins that Modulate Ionic Channels as Tools for Exploring Insulin Secretion
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Glucose-induced insulin secretion is a cardinal process in glucose homeostasis and metabolic expenditure. Uncoupling of the insulin response to glucose variations may lead to type-2 diabetes mellitus. Thus the identification of more specific drugs to facilitate the study of insulin secretion mechanisms and to develop new pharmacological agents for therapeutics is fundamental. Venomous organisms possess a great diversity of toxic molecules and some of them are neurotoxins that affect membrane excitability. This article reviews properties of those toxins affecting ion channels pivotal for insulin secretion and the usefulness of such compounds in the study of pancreatic beta-cell physiology. Here we examine the major contributions of toxinology to the understanding of the ionic phase of insulin secretion, to the determination of ion channel composition in different insulin secreting cell-line models as well as from primary cultures of different mammal species. Finally, we present a summary of the many diverse toxins affecting insulin release and a brief discussion of the potential of novel toxins in therapeutics.
KeywordsNa channels Ca channels KATP channels Pancreatic beta cells
We are grateful to, Dr. Tamara Rosenbaum for reading and discussing the manuscript. To Ana María Escalante Gonzalbo and Francisco Pérez Eugenio, from the Computer Unit and Felix Sierra, for excellent technical support. All from the Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, UNAM. This work was supported by Gobierno del Distrito Federal PICDS08-72, CONACYT FI 60065, DGAPA-PAPIIT 229407, and SDI.PTID. 05.6 Facultad de Medicina Universidad Nacional Autónoma de México. Carlos Manlio Díaz García received scholar grants from Doctorado Conjunto en Ciencias Biológicas UNAM-UH, Red de Macro Universidades de América Latina y el Caribe and Gobierno del Distrito Federal PICDS08-72.
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