Flipped zinc transporter 8 (ZnT8): a novel approach to characterize zinc transport and its possible relevance to type 2 diabetes

UnrestrictedZinc is an essential trace element in living organisms, and zinc content in pancreatic β-cells is amongst the highest in the body. Zinc transporter 8 (ZnT8) is localized to the insulin vesicle membrane and is responsible for transporting zinc from the cytoplasm into the vesicles. Inside the vesicles, zinc is hypothesized to crystallize with insulin in a physiologically important process. Interestingly, recent genome-wide association studies have identified a non-synonymous single nucleotide polymorphism (SNP) in the gene encoding ZnT8 that is highly associated with the development of type 2 diabetes. However, to date, no studies have been capable of analyzing the effects of the SNP on ZnT8 function. We have designed a flipped ZnT8 that can be used to monitor cytoplasmic zinc influx using the fluorescent zinc indicator, Fluozin-3-AM. This appears to be a promising method for directly analyzing the functional consequences of the ZnT8 T2D-associated SNP