Genetic, Functional, and Immunological Study of ZnT8 in Diabetes

الملخص EN

Zinc level in the body is finely regulated to maintain cellular function.

Dysregulation of zinc metabolism may induce a variety of diseases, e.g., diabetes.

Zinc participates in insulin synthesis, storage, and secretion by functioning as a “cellular second messenger” in the insulin signaling pathway and glucose homeostasis.

The highest zinc concentration is in the pancreas islets.

Zinc accumulation in cell granules is manipulated by ZnT8, a zinc transporter expressed predominately in pancreatic α and β cells.

A common ZnT8 gene (SLC30A8) polymorphism increases the risk of type 2 diabetes mellitus (T2DM), and rare mutations may present protective effects.

In type 1 diabetes mellitus (T1DM), autoantibodies show specificity for binding two variants of ZnT8 (R or W at amino acid 325) dictated by a polymorphism in SLC30A8.

In this review, we summarize the structure, feature, functions, and polymorphisms of ZnT8 along with its association with diabetes and explore future study directions.