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

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.

脂联素与胰岛β细胞功能关系的研究进展

脂联素是由脂肪细胞分泌的一种重要肽激素,能够调节新陈代谢和能量平衡。脂联素可引起脂肪酸氧化、促进葡萄糖摄取,并在肌肉和肝脏中抑制糖异生,由此改善胰岛素的敏感性。此外,脂联素还有抗动脉粥样硬化及抗炎作用。大多数研究集中于脂联素在骨骼肌、肝脏和脂肪组织中的作用,而对脂联素与胰岛β细胞之间关联的可靠研究结果相对较少。该文旨在阐述脂联素与胰岛β细胞间的复杂关系。