Role of cytosolic and endoplasmic reticulum Ca in pancreatic beta-cells: pros and cons.

Pancreatic beta cells utilize Ca to secrete insulin in response to glucose. The glucose-dependent increase in cytosolic Ca concentration ([Ca]) 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 [Ca]-dependent manner, at least within a moderate range. However, the demand for insulin secretion may surpass the capability of beta cells. Abnormal elevation of [Ca] 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 Ca 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 [Ca] is inevitable under certain hazardous conditions, understanding the regulatory mechanism for [Ca] is important. Therefore, this review discusses beta-cell function, survival, ER stress, and apoptosis associated with intracellular and ER Ca homeostasis.