TY - JOUR T1 - Modulation of ionic channels and insulin secretion by drugs and hormones in pancreatic beta cells JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.116.103861 SP - mol.116.103861 AU - Myrian Velasco AU - Carlos Manlio Diaz-Garcia AU - Carlos Larque AU - Marcia Hiriart Y1 - 2016/01/01 UR - http://molpharm.aspetjournals.org/content/early/2016/07/19/mol.116.103861.abstract N2 - Pancreatic beta cells play a significant role in glucose homeostasis; they are the unique cells that secrete insulin in response to an increase in glucose levels. Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells has been extensively explored. In this mechanism, glucose enters the cells and then the metabolic cycle; during this process the ATP/ADP ratio increase, leading to the closure of KATP channels. KATP channels closure initiates depolarization, which is also dependent on the activity of TRP non-selective ion channels. Depolarization leads to the opening of voltage-gated Na+ channels (Nav) and subsequently voltage-dependent Ca2+ channels (Cav). The increase in intracellular Ca2+ triggers the exocytosis of insulin-containing vesicles. Thus, electrical activity of pancreatic beta cells plays a central role in GSIS. Moreover, many growth factors, incretins, neurotransmitters, and hormones can modulate it. All the channels that participate in GSIS are highly regulated. In this review, we focus on the principal ionic channels (KATP, Nav, and Cav channels) involved in GSIS, and how do classic and new proteins, hormones, and drugs regulate them. Moreover, we also discuss some advances on how metabolic disorders such as metabolic syndrome and diabetes mellitus change channel activity leading to changes in insulin secretion. ER -