Zinc transporters and their role in the pancreatic β‐cell

Zinc is an essential nutrient with tremendous importance for human health, and zinc deficiency is a severe risk factor for increased mortality and morbidity. As abnormal zinc homeostasis causes diabetes, and because the pancreatic β‐cell contains the highest zinc content of any known cell type, it is of interest to know how zinc fluxes are controlled in β‐cells. The understanding of zinc homeostasis has been boosted by the discovery of multiprotein families of zinc transporters, and one of them – zinc transporter 8 (ZnT8) – is abundantly and specifically expressed in the pancreatic islets of Langerhans. In this review, we discuss the evidence for a physiological role of ZnT8 in the formation of zinc‐insulin crystals, the physical form in which most insulin is stored in secretory granules. In addition, we cross‐examine this information, collected in genetically modified mouse strains, to the knowledge that genetic variants of the human ZnT8 gene predispose to the onset of type 2 diabetes and that epitopes on the ZnT8 protein trigger autoimmunity in patients with type 1 diabetes. The overall conclusion is that we are still at the dawn of a complete understanding of how zinc homeostasis operates in normal β‐cells and how abnormalities lead to β‐cell dysfunction and diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00199.x, 2012)