New antigenic targets in type 1 diabetes.
OBJECTIVE
The beta-cell-specific zinc transporter isoform 8 (SLC30A8) has recently emerged both as a major autoantigenic target of type 1 diabetes and also as a genetic marker for type 2 diabetes. We examine the hypothesis that the cell specificity and cellular localization of this granule membrane protein are significant factors in its contribution to the pathogenesis of these diseases.


RESULTS
Both type 1 diabetes and type 2 diabetes are associated with islet functional failure and both diseases may be linked to stress responses and changes in the secretory pathway, which lead to cell apoptosis and thus directly to reduction of beta-cell mass or activation of underlying autoimmunity. In both cases, the common polymorphism at aa 325 has been implicated in disease, in type 1 diabetes by determining the autoantibody epitope specificity and in type 2 diabetes through association with altered beta-cell mass and impaired secretion.


CONCLUSIONS
Functional studies of the transporter will be key to understanding the role of ZnT8 in type 2 diabetes. Investigation of the cellular immune response to ZnT8 will be essential in evaluating its contribution to type 1 diabetes. Measurement of autoantibodies to ZnT8 takes us a step closer to detection of prediabetes in the general population.
Wenzlau
Janet M
JM
Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045, USA.
Hutton
John C
JC
Davidson
Howard W
HW
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D027682:Cation Transport Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000276:immunology; D006801:Humans; D000075703:Zinc Transporter 8
D001323:Autoantibodies; D001324:Autoantigens; D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8