Ca2+ release or Ca2+ entry, that is the question: what governs Ca2+ oscillations in pancreatic β cells?

Abstract

The standard model for Ca2+ oscillations in insulin-secreting pancreatic β cells centers on Ca2+ entry through voltage-activated Ca2+ channels. These work in combination with ATP-dependent K+ channels, which are the bridge between the metabolic state of the cells and plasma membrane potential. This partnership underlies the ability of the β cells to secrete insulin appropriately on a minute-to-minute time scale to control whole body plasma glucose. Though this model, developed over more than 40 years through many cycles of experimentation and mathematical modeling, has been very successful, it has been challenged by a hypothesis that calcium-induced calcium release from the endoplasmic reticulum through ryanodine or inositol trisphosphate (IP3) receptors is instead the key driver of islet oscillations. We show here that the alternative model is in fact incompatible with a large body of established experimental data and that the new observations offered in support of it can be better explained by the standard model.