Calcium signaling in pancreatic β-cells in health and in Type 2 diabetes

Changes in cytosolic free Ca2+ concentration ([Ca2+](c)) play a crucial role in the control of insulin secretion from the electrically excitable pancreatic beta-cell. Secretion is controlled by the finely tuned balance between Ca2+ influx (mainly through voltage-dependent Ca2+ channels, but also through voltage-independent Ca2+ channels like store-operated channels) and efflux pathways. Changes in [Ca2+], directly affect [Ca2+] in various organelles including the endoplasmic reticulum (ER), mitochondria, the Golgi apparatus, secretory granules and lysosomes, as imaged using recombinant targeted probes. Because most of these organelles have specific Ca2+ influx and efflux pathways, they mutually influence free [Ca2+] in the others. In this article, we review the mechanisms of control of [Ca2+] in various compartments and particularly the cytosol, the endoplasmic reticulum ([Ca2+](ER)), acidic stores and mitochondrial matrix ([Ca2+](mito)), focusing chiefly on the most important physiological stimulus of beta-cells, glucose. We also briefly review some alterations of beta-cell Ca2+ homeostasis in Type 2 diabetes. (C) 2014 Elsevier Ltd. All rights reserved.