title: Zn(2+)-transporter-8: a dual role in diabetes.
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.
authors: Department of Molecular Diagnostics, National Research Center GosNIIgenetika, Moscow, Russia. dimitry.chistiakov@lycos.com
authors: Dimitry A
authors: DA
authors: Chistiakov
authors: Natalia V
authors: NV
authors: Voronova
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics / Q000502:physiology*; D003920:Diabetes Mellitus / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D015032:Zinc / Q000502:physiology; D000075703:Zinc Transporter 8
chemical_list: D027682:Cation Transport Proteins; D007328:Insulin; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D015032:Zinc