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

• Changes in [Ca2+]c control insulin secretion from pancreatic β-cells.
• Cell metabolism affects [Ca2+] in all compartments of β-cells.
• Changes in [Ca2+]c directly controls [Ca2+]mito and cell metabolism in β-cells.
• The ER and the cytosol mutually affect their [Ca2+] β-cells.
• Alterations of β-cell Ca2+ homeostasis are observed 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 β-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+]c 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 β-cells, glucose. We also briefly review some alterations of β-cell Ca2+ homeostasis in Type 2 diabetes.

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