The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes

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The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes.

Type 1 diabetes (T1D) results from progressive loss of pancreatic islet mass through autoimmunity targeted at a diverse, yet limited, series of molecules that are expressed in the pancreatic beta cell. Identification of these molecular targets provides insight into the pathogenic process, diagnostic assays, and potential therapeutic agents. Autoantigen candidates were identified from microarray...

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ZnT8 Is a Major CD8+ T Cell–Recognized Autoantigen in Pediatric Type 1 Diabetes

Type 1 diabetes results from the destruction of β-cells by an autoimmune T-cell response assisted by antigen-presenting B cells producing autoantibodies. CD8(+) T-cell responses against islet cell antigens, thought to play a central role in diabetes pathogenesis, can be monitored using enzyme-linked immunosorbent spot (ELISpot) assays. However, such assays have been applied to monitoring of adu...

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A Common Nonsynonymous Single Nucleotide Polymorphism in the SLC30A8 Gene Determines ZnT8 Autoantibody Specificity in Type 1 Diabetes

OBJECTIVE Zinc transporter eight (SLC30A8) is a major target of autoimmunity in human type 1A diabetes and is implicated in type 2 diabetes in genome-wide association studies. The type 2 diabetes nonsynonymous single nucleotide polymorphism (SNP) affecting aa(325) lies within the region of highest ZnT8 autoantibody (ZnT8A) binding, prompting an investigation of its relationship to type 1 diabet...

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SLC30A8 (ZnT8) variations and type 2 diabetes in the Chinese Han population.

In recent genome-wide association studies, variants in the SLC30A8 gene have been found to be associated with risk for type 2 diabetes. We examined a possible association of tag SNPs spanning SLC30A8 and their haplotypes with type 2 diabetes in the Chinese Han population. There were 1508 Chinese Han type 2 diabetes patients and 1500 age- and gender-matched control subjects; all were genoty...

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The Zinc Transporter Slc30a8/ZnT8 Is Required in a Subpopulation of Pancreatic α-Cells for Hypoglycemia-induced Glucagon Secretion*

SLC30A8 encodes a zinc transporter ZnT8 largely restricted to pancreatic islet β- and α-cells, and responsible for zinc accumulation into secretory granules. Although common SLC30A8 variants, believed to reduce ZnT8 activity, increase type 2 diabetes risk in humans, rare inactivating mutations are protective. To investigate the role of Slc30a8 in the control of glucagon secretion, Slc30a8 was i...

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ژورنال

عنوان ژورنال: Proceedings of the National Academy of Sciences

سال: 2007

ISSN: 0027-8424,1091-6490

DOI: 10.1073/pnas.0705894104