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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #345922

Research Project: Novel Functions and Biomarkers for Vitamins and Minerals

Location: Obesity and Metabolism Research

Title: SLC30A family expression in the pancreatic islets of humans and mice: cellular localization in the ß-cells

Author
item Cai, Yimeng - University Of California, Davis
item Kirschke, Catherine
item Huang, Liping

Submitted to: Journal of Molecular Histology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/27/2017
Publication Date: 1/25/2018
Citation: Cai, Y., Kirschke, C.P., Huang, L. 2018. SLC30A family expression in the pancreatic islets of humans and mice: cellular localization in the ß-cells. Journal of Molecular Histology. 49(2):133-145. https://doi.org/10.1007/s10735-017-9753-0.
DOI: https://doi.org/10.1007/s10735-017-9753-0

Interpretive Summary: Zinc is a vital co-factor for insulin metabolism in the pancreatic ß-cell, including synthesis, maturation, and crystallization. Two families of zinc transporters, namely SLC30 (ZNT) and SLC39 (ZIP) are involved in maintaining zinc levels in a narrow physiological range in a given cell. Single nuclear polymorphisms (SNPs; changes in nucleotides in the genomic DNA) or mutations (nucleotide changes that destroy protein function) in zinc transporters have been associated with insulin resistance and risks of type 2 diabetes (T2D) in both humans and mice. Thus, mice can be useful for studying the underlying mechanisms of zinc-associated risks of T2D or T2D development. To determine potential differences in zinc transporter expression and expressed locations in the pancreatic ß-cells between humans and mice, we examined all members (ZNT1-10) of the ZNT family in pancreatic islets and in ß-cell lines derived from both species using antibodies and fluorescence microscopy. We found that there were no substantial differences in the expression of 9 ZNT proteins in human and mouse islets and ß-cells. ZNT3 was only detected in human ß-cells, but not in mouse ß-cells. Moreover, we found that ZNT2 was localized on the cell surface of both human and mouse ß-cells, suggesting a role of ZNT2 in direct export of zinc out of the ß-cell. Together, our study demonstrates that there is functional conservation of ZNT proteins between humans and mice. We believe that mice with abnormal zinc metabolism either by genetic or nutritional modifications can be used for studying mechanisms of zinc-associated risk of T2D in humans.

Technical Abstract: Zinc is a vital co-factor for insulin metabolism in the pancreatic ß-cell, including synthesis, maturation, and crystallization. Two families of zinc transporters, namely SLC30 (ZNT) and SLC39 (ZIP) are involved in maintaining cellular zinc homeostasis in mammalian cells. Single nuclear polymorphisms (SNPs) or mutations in zinc transporters have been associated with insulin resistance and risks of type 2 diabetes (T2D) in both humans and mice. Thus, mice can be useful for studying the underlying mechanisms of zinc-associated risks of T2D or T2D development. To determine potential differences in zinc transporter expression and cellular localization in the pancreatic ß-cells between humans and mice, we examined all members (ZNT1-10) of the ZNT family in pancreatic islets and in ß-cell lines derived from both species using immunohistochemistry and immunofluorescence microscopic analysis. We found that there were no substantial differences in the expression of 9 ZNT proteins in human and mouse islets and ß-cells. ZNT3 was only detected in human ß-cells, but not in mouse ß-cells. Moreover, we found that ZNT2 was localized on the cell surface of both human and mouse ß-cells, suggesting a role of ZNT2 in direct export of zinc out of the ß-cell. Together, our study demonstrates that there is functional conservation of ZNT proteins between humans and mice. We believe that mice with abnormal zinc metabolism either by genetic or nutritional modifications can be used for studying mechanisms of zinc-associated risk of T2D in humans.