Zn(2+)-transporter-8: a dual role in diabetes

Biofactors. 2009 Jul-Aug;35(4):356-63. doi: 10.1002/biof.49.

Abstract

Diabetes mellitus arises from defects in insulin secretion or action, or both. In pancreatic islets, insulin production is linked with zinc transport mediated by zinc transporter ZnT-8, a product of the SLC30A8 gene. Therefore, altered activity of ZnT-8 is expected to be associated with impaired glucose-induced insulin response and promote progression from glucose intolerance to diabetes. Recent findings do emerge with a role of SLC30A8 in diabetes. Genome-wide association scans for type 2 diabetes (T2D) susceptibility loci revealed and then replicated a highly significant association between the R allele of the R325W variant of SLC30A8 (marker rs13266634) and susceptibility to T2D in Caucasians. A role of ZnT-8 as a new major self-antigenic determinant in type 1 diabetes (T1D) was found. Marker rs13266634 was also shown to modulate anti-ZnT-8 self-antibody specificity in islet autoimmunity. Hence, these findings suggest for a dual role of SLC30A8 in diabetes, which is consisted in conferring genetic susceptibility to T2D and being a major islet self-antigen in T1D as well. Here we characterize an emerging role of ZnT-8 in diabetes and discuss potential mechanisms of its involvement in the etiology of both forms of diabetes.

Publication types

  • Review

MeSH terms

  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / physiology*
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 2 / genetics
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Zinc / physiology
  • Zinc Transporter 8

Substances

  • Cation Transport Proteins
  • Insulin
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • Zinc