The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression

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• 作者：Kamille Smidt ; Agnete Larsen ; Andreas Brønden ; Karen S. Sørensen…
• 关键词：ZNT3 ; SLC30A3 ; ZNT8 ; Localization ; Insulin secretion ; Beta cell survival
• 刊名：Biometals
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：29
• 期：2
• 页码：287-298
• 全文大小：1,055 KB
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• 作者单位：Kamille Smidt (1) (2)
  Agnete Larsen (1)
  Andreas Brønden (4)
  Karen S. Sørensen (1)
  Julie V. Nielsen (1)
  Jeppe Praetorius (1)
  Pia M. Martensen (3)
  Jørgen Rungby (1) (4) (5)
  
  1. Department of Biomedicine, Aarhus University, Århus, Denmark
  2. Department of Clinical Medicine, Aarhus University, Palle Juul-Jensen Boulevard 82, 8200, Århus N, Denmark
  4. Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
  3. Department of Molecular Biology and Genetics, Aarhus University, Århus, Denmark
  5. Department of Clinical Pharmacology, Rigshospitalet, Copenhagen, Denmark
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Physical Chemistry
  
• 出版者：Springer Netherlands
• ISSN：1572-8773

文摘

Zinc trafficking in pancreatic beta cells is tightly regulated by zinc transporting (ZNTs) proteins. The role of different ZNTs in the beta cells is currently being clarified. ZNT8 transports zinc into insulin granules and is critical for a correct insulin crystallization and storage in the granules whereas ZNT3 knockout negatively affects beta cell function and survival. Here, we describe for the first time the sub-cellular localization of ZNT3 by immuno-gold electron microscopy and supplement previous data from knockout experiments with investigations of the effect of ZNT3 in a pancreatic beta cell line, INS-1E overexpressing ZNT3. In INS-1E cells, we found that ZNT3 was abundant in insulin containing granules located close to the plasma membrane. The level of ZNT8 mRNA was significantly decreased upon over-expression of ZNT3 at different glucose concentrations (5, 11 and 21 mM glucose). ZNT3 over-expression decreased insulin content and insulin secretion whereas ZNT3 over-expression improved the cell survival after 24 h at varying glucose concentrations (5, 11 and 21 mM). Our data suggest that ZNT3 and ZNT8 (known to regulate insulin secretion) have opposite effects on insulin synthesis and secretion possibly by a transcriptional co-regulation since mRNA expression of ZNT3 was inversely correlated to ZNT8 and ZNT3 over-expression reduced insulin synthesis and secretion in INS-1E cells. ZNT3 over-expression improved cell survival.