Diabetes-linked zinc transporter ZnT8 is a homodimeric protein expressed by distinct rodent endocrine cell types in the pancreas and other glands

Abstract Background and aims Zinc is abundant in pancreas, being required by endocrine islet cells for hormone secretion and by exocrine acinar cells as pancreatic juice component. ZnT8 is a member of the SLC30A family of zinc transporters whose overexpression in cultured pancreatic β cells leads to...

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Published in:Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2009-07, Vol.19 (6), p.431-439
Main Authors: Murgia, C, Devirgiliis, C, Mancini, E, Donadel, G, Zalewski, P, Perozzi, G
Format: Article
Language:English
Subjects:
Adrenal Cortex - metabolism
Adrenal gland
Animals
Caco-2 Cells
Cardiovascular
Cation Transport Proteins - genetics
Cation Transport Proteins - metabolism
Cell Membrane - metabolism
Cercopithecus aethiops
COS Cells
Diabetes Mellitus - metabolism
Dogs
Endocrine cells
Humans
Insulin
Mice
Pancreas - metabolism
Protein Multimerization
Rats
T2D
Thyroid
Thyroid Gland - metabolism
Transfection
Zinc Transporter 8
Zn transport
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Summary:Abstract Background and aims Zinc is abundant in pancreas, being required by endocrine islet cells for hormone secretion and by exocrine acinar cells as pancreatic juice component. ZnT8 is a member of the SLC30A family of zinc transporters whose overexpression in cultured pancreatic β cells leads to increased insulin secretion in response to glucose, suggesting a possible role in regulating glycemia. ZnT8 was therefore proposed as a therapeutic target for diabetes, and recent genome-wide association studies identified polymorphisms in the ZNT8 gene conferring increased type 2 diabetes risk. Methods and results As limited information was available on the biochemical properties of ZnT8 and on its endogenous expression, we have raised a specific polyclonal antibody and immunostained protein extracts, cell lines and tissue sections. We show that ZnT8 forms a very stable dimer that requires biological membranes to properly assemble. We demonstrate localization of murine ZnT8 to the secretory granules in pancreatic β and α islet cells. Moreover, we show that ZnT8 is also expressed in other secretory cell types, namely the cubical epithelium that lines thyroid follicles and the cortex of the adrenal gland, suggesting a more widespread role in endocrine secretion. Conclusion We provide novel insights into the features of the ZnT8 transporter, of special relevance in light of its proposed role as therapeutical target for diabetes treatment.
ISSN:0939-4753
1590-3729
DOI:10.1016/j.numecd.2008.09.004