siRNA-mediated knock-down of ZnT3 and ZnT8 affects production and secretion of insulin and apoptosis in INS-1E cells

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2011-02, Vol.119 (2), p.93-102
• Main Authors: PETERSEN, ANDREAS B, SMIDT, KAMILLE, MAGNUSSON, NILS E, MOORE, FABRICE, EGEFJORD, LÆRKE, RUNGBY, JØRGEN
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biological and medical sciences; Cation Transport Proteins - antagonists & inhibitors; Cation Transport Proteins - genetics; Cation Transport Proteins - physiology; Cells, Cultured; diabetes; Fundamental and applied biological sciences. Psychology; Infectious diseases; insulin; Insulin - biosynthesis; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Medical sciences; Microbiology; Rats; RNA, Small Interfering - genetics; siRNA; Zinc; zinc transporter; Zinc Transporter 8
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/j.1600-0463.2010.02698.x

Petersen AB, Smidt K, Magnusson NE, Moore F, Egefjord L, Rungby J. siRNA-mediated knock-down of ZnT3 and ZnT8 affects production and secretion of insulin and apoptosis in INS-1E cells. APMIS 2010; 119: 93-102. Zinc is essential for the crystallization of insulin in pancreatic β-cells and is thought to induce apoptosis in a dose-dependent manner, thereby regulating β-cell mass. Therefore, a tight intracellular regulation of Zn²⁺ is required. The zinc-transporter family SLC30A is an important factor in the regulation of zinc homeostasis. The aim of this study was to examine the effect of the zinc transporters ZnT3 and ZnT8 on insulin metabolism and apoptosis. Both these proteins are present in pancreatic β-cells and have been linked to diabetes. The objective of our study was to perform a considerable siRNA-mediated knock-down of ZnT3 and ZnT8 in INS-1E cells, a pancreatic β-cell model, and afterwards examine the impact on cell viability and insulin metabolism. Increased levels of apoptosis were observed after knock-down of both ZnT3 and ZnT8. Insulin secretion was significantly reduced by ZnT3 knock-down, whereas knock-down of ZnT8 resulted in increased intracellular content of insulin accompanied by a relatively lowered secretion. Both zinc transporters in this way seem to play a role in β-cell survival and the ability of these cells to react appropriately to surrounding glucose concentrations.