Metabolic regulation of calcium signaling in beta cells.

The cytoplasmic Ca2+ concentration ([Ca2+]cyt) regulates a vast number of cellular functions, including insulin secretion from beta cells. The major physiological insulin secretagogue, glucose, triggers [Ca2+]cyt oscillations in beta cells. Synchronization of the oscillations among the beta cells within an islet underlies the generation of pulsatile insulin secretion. This review describes the mechanisms generating [Ca2+]cyt oscillations, the interactions between [Ca2+]cyt and cell metabolism, as well as the contribution of various organelles to the shaping of [Ca2+]cyt signals and insulin secretion. It also discusses how Ca2+ signals are coordinated and spread throughout the islets and data indicating that altered Ca2+ signaling is associated with beta cell dysfunction and development of type 2 diabetes.