| First Author | Wang X | Year | 2019 |
| Journal | Protein Cell | Volume | 10 |
| Issue | 6 | Pages | 436-449 |
| PubMed ID | 30324491 | Mgi Jnum | J:279170 |
| Mgi Id | MGI:6356270 | Doi | 10.1007/s13238-018-0580-1 |
| Citation | Wang X, et al. (2019) The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic beta-cells via Sirt1- and Pgc-1alpha-mediated regulation of Glut2. Protein Cell 10(6):436-449 |
| abstractText | Zinc levels are high in pancreatic beta-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 beta-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 down-regulated in pancreatic beta-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, beta-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-1alpha and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1alpha and Ppar-gamma. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1alpha activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions. |
