Zinc and insulin in pancreatic beta-cells

Endocrine. 2014 Mar;45(2):178-89. doi: 10.1007/s12020-013-0032-x. Epub 2013 Aug 24.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Homeostasis / physiology*
  • Humans
  • Insulin / physiology*
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / physiology*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / physiology
  • Models, Animal
  • Paracrine Communication / physiology
  • Signal Transduction / physiology
  • Zinc / physiology*


  • Insulin
  • Zinc