Volume 10 Issue 6
Jun.  2019
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Article Contents
Xinhui Wang, Hong Gao, Wenhui Wu, Enjun Xie, Yingying Yu, Xuyan He, Jin Li, Wanru Zheng, Xudong Wang, Xizhi Cao, Zhuoxian Meng, Ligong Chen, Junxia Min, Fudi Wang. The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1-and Pgc-1α-mediated regulation of Glut2[J]. Protein&Cell, 2019, 10(6): 436-449. doi: 10.1007/s13238-018-0580-1
Citation: Xinhui Wang, Hong Gao, Wenhui Wu, Enjun Xie, Yingying Yu, Xuyan He, Jin Li, Wanru Zheng, Xudong Wang, Xizhi Cao, Zhuoxian Meng, Ligong Chen, Junxia Min, Fudi Wang. The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1-and Pgc-1α-mediated regulation of Glut2[J]. Protein&Cell, 2019, 10(6): 436-449. doi: 10.1007/s13238-018-0580-1

The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1-and Pgc-1α-mediated regulation of Glut2

doi: 10.1007/s13238-018-0580-1

31570791 and 91542205 to J. Min), the National Key R&D Program of China (2018YFA0507801 to J. Min and 2018YFA0507802 to F. Wang), the Zhejiang Provincial Natural Science Foundation of China (LQ15C110002 to X. Wang and LZ15H160002 to J. Min) and the Nation Science and Technology Major Projects for Major New Drugs Innovation and Develop 2017ZX09101-005-004-002 (L. Chen).

31530034 and 31330036 to F. Wang

This study was supported by research grants from the National Natural Science Foundation of China (31600953 to X. Wang

  • Received Date: 2018-06-28
  • Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly downregulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.
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