Role of cytosolic and endoplasmic reticulum Ca2+ in pancreatic beta-cells: pros and cons

Pancreatic beta cells utilize Ca2+ to secrete insulin in response to glucose. The glucose-dependent increase in cytosolic Ca2+ concentration ([Ca2+](C)) activates a series of insulin secretory machinery in pancreatic beta cells. Therefore, the amount of insulin secreted in response to glucose is determined in a [Ca2+](C)-dependent manner, at least within a moderate range. However, the demand for insulin secretion may surpass the capability of beta cells. Abnormal elevation of [Ca2+](C) levels beyond the beta-cell endurance capacity can damage them by inducing endoplasmic reticulum (ER) stress and cell death programs such as apoptosis. Therefore, while Ca2+ is essential for the insulin secretory functions of beta cells, it could affect their survival at pathologically higher levels. Because an increase in beta-cell [Ca2+](C) is inevitable under certain hazardous conditions, understanding the regulatory mechanism for [Ca2+](C) is important. Therefore, this review discusses beta-cell function, survival, ER stress, and apoptosis associated with intracellular and ER Ca2+ homeostasis.