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

    1. Florent Allagnat2
    1. 1Signalisation et Physiopathologie Cardiovasculaire, Inserm UMR-S 1180-LabEx LERMIT, Faculté de Pharmacie, Châtenay-Malabry France
    2. 2Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    1. Correspondence should be addressed to F Allagnat; Email: florent.allagnat{at}


    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.

    • Received 8 July 2016
    • Accepted 2 September 2016
    • Made available online as an Accepted Preprint 2 September 2016
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