title: Store-operated Ca2+ entry: a key component of the insulin secretion machinery.
abstract: 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 (KATP), 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.
authors: Signalisation et Physiopathologie CardiovasculaireInserm UMR-S 1180-LabEx LERMIT, Faculté de Pharmacie, Châtenay-Malabry France.
authors: Jessica
authors: J
authors: Sabourin
authors: Department of Vascular SurgeryCentre Hospitalier Universitaire Vaudois, Lausanne, Switzerland florent.allagnat@chuv.ch.
authors: Florent
authors: F
authors: Allagnat
keywords: Orai1; STIM1; TRPC1; insulin secretion; pancreatic β-cells; store-operated Ca2+ entry