Zinc Transporter 8 (ZnT8) Autoantibody ELISA Kit

Zinc transporter 8 (ZNT8) is a transmembrane transporter protein in humans that is encoded by the SLC30A8 gene and contains 369 amino acids. Zinc deficiency, an essential trace element, can lead to a variety of disorders with a poor prognosis, including diabetes, cancer, and Alzheimer's. In the human insulin production pathway, zinc is essential for proinsulin processing and packaging. ZNT8 is principally important for delivering Zn2+ from the cytoplasm to insulin vesicles, ensuring that zinc accumulates in insulin secretory granules (ISGs). Therefore, ZNT8 expression is limited to the insulin secretory granules of pancreatic β-cells. ZNT8 plays an important role in pancreatic β-cell function by facilitating insulin storage and secretion. Insulin, a hormone that regulates blood glucose levels, is stored in ISGs, where ZNT8 ensures adequate zinc levels to support insulin hexamer formation. Without enough ZNT8 activity, zinc levels in ISGs fall, resulting in incorrect insulin packing and secretion, which can disrupt glucose homeostasis.

Figure 1. Schematic of ZnT8 protein with cytoplasmic C-terminus.(Source: Skärstrand H, et al., 2013)

ZNT8 dysfunction is linked to autoimmune disorders, specifically type 1 and type 2 diabetes. When the immune system is dysregulated, immune cells (such as B lymphocytes) may wrongly recognize and target the ZNT8 protein in islet cells, resulting in aberrant insulin production and a disruption in blood glucose homeostasis. Furthermore, the immune system's attack on ZNT8 can cause an inflammatory reaction, affecting the function and structure of insulin-producing cells and aggravating the diabetic pathology. ZNT8 has been discovered as a significant autoantigen in type 1 diabetes, and autoantibodies to ZNT8 (ZnT8A) have emerged as a promising diagnostic for the diagnosis of T1DM. ZnT8A often occurs before clinical symptoms, making it a useful tool for early detection and risk stratification. Data show that ZnT8A can detect roughly 70% of young T1DM patients.

However, ZNT8 may have different functions in T1DM and T2DM. Certain loss-of-function mutations in the ZNT8 gene (such as the R325W mutation) reduce ZNT8 activity, however the effect on insulin secretion is not necessarily negative. Researchers have identified 12 uncommon loss-of-function mutations caused by ZNT8 truncation that can minimize aberrant insulin production or improve insulin activity, lowering the risk of type 2 diabetes by 65%. These findings imply that moderate modulation of ZNT8 function could be a novel method for preventing and treating type 2 diabetes. Furthermore, knowing the genetic and molecular pathways that underpin ZNT8 function and its role in diabetes provides important insights into prospective treatment approaches. The dual nature of ZNT8 in various types of diabetes highlights the intricacy of its activity and the necessity for personalized therapy solutions. Targeting ZNT8, either by regulating its activity or using it as a biomarker, opens up new possibilities for early detection and individualized treatment in diabetes control.

ZnT8 autoantibody assay
ZnT8 antibody ELISA kit
Autoantibody detection kit for ZnT8