Store-operated Ca2+ entry: a key component of the insulin secretion machinery

Normal plasma glucose level is ensured by the action of insulin, the major hypoglycemic hormone. Therefore, it is not surprising that insulin release from pancreatic β-cells of the islets of Langerhans is controlled by an array of balanced mechanisms in which glucose plays the leading role. Glucose triggers insulin secretion through the well-described pathway of ATP-driven closure of ATP-sensitive potassium channels (K_ATP), depolarization of the plasma membrane, and opening of the voltage-dependent Ca²⁺ channels (VDCC). The subsequent rapid rise in cytoplasmic free Ca²⁺ concentration triggers insulin exocytosis. However, despite more than 40 years of investigation, certain aspects of the intracellular Ca²⁺ responses to glucose and secretagogues remain unexplained, suggesting the involvement of additional Ca²⁺ channels. Here, we discuss the emerging role of store-operated Ca²⁺ channels carried by Orai1 and transient receptor potential canonical 1 (TRPC1) proteins and regulated by the stromal interaction molecule 1 (STIM1) in the control of glucose-induced insulin secretion. The role of other voltage-independent cation channels formed by other members of the TRP channels family is also addressed.