Zinc and insulin in pancreatic beta-cells

Zinc (Zn²⁺) is an essential element crucial for growth and development, and also plays a role in cell signaling for cellular processes like cell division and apoptosis. In the mammalian pancreas, Zn²⁺ is essential for the correct processing, storage, secretion, and action of insulin in beta (β)-cells. Insulin is stored inside secretory vesicles or granules, where two Zn²⁺ ions coordinate six insulin monomers to form the hexameric-structure on which maturated insulin crystals are based. The total Zn²⁺ content of the mammalian pancreas is among the highest in the body, and Zn²⁺ concentration reach millimolar levels in the interior of the dense-core granule. Changes in Zn²⁺ levels in the pancreas have been found to be associated with diabetes. Hence, the relationship between co-stored Zn²⁺ and insulin undoubtedly is critical to normal β-cell function. The advances in the field of Zn²⁺ biology over the last decade have facilitated our understanding of Zn²⁺ trafficking, its intracellular distribution and its storage. When exocytosis of insulin occurs, insulin granules fuse with the β-cell plasma membrane and release their contents, i.e., insulin as well as substantial amount of free Zn²⁺, into the extracellular space and the local circulation. Studies increasingly indicate that secreted Zn²⁺ has autocrine or paracrine signaling in β-cells or the neighboring cells. This review discusses the Zn²⁺ homeostasis in β-cells with emphasis on the potential signaling role of Zn²⁺ to islet biology.