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New antigenic targets in type 1 diabetes

Wenzlau, Janet M; Hutton, John C; Davidson, Howard W

Current Opinion in Endocrinology, Diabetes and Obesity: August 2008 - Volume 15 - Issue 4 - p 315–320
doi: 10.1097/MED.0b013e328308192b
Diabetes and the endocrine pancreas II: Edited by Peter A. Gottlieb
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Purpose of review The β-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.

Recent findings 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 β-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 β-cell mass and impaired secretion.

Summary 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.

Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado, USA

Correspondence to Dr John C. Hutton, PhD, Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver and Health Sciences Center, PO Box 6511, 1775 North Ursula Street, Aurora, CO 80045, USA Tel: +1 303 724 6837; fax: +1 303 724 6839; e-mail: John.Hutton@uchsc.edu

© 2008 Lippincott Williams & Wilkins, Inc.