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.