| First Author | Chen WB | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 36 | Pages | 57485-57497 |
| PubMed ID | 27542279 | Mgi Jnum | J:317387 |
| Mgi Id | MGI:6832116 | Doi | 10.18632/oncotarget.11295 |
| Citation | Chen WB, et al. (2016) Conditional ablation of HDAC3 in islet beta cells results in glucose intolerance and enhanced susceptibility to STZ-induced diabetes. Oncotarget 7(36):57485-57497 |
| abstractText | Histone deacetylases (HDACs) are enzymes that regulate gene expression by modifying chromatin structure through removal of acetyl groups from target histones or non-histone proteins. Previous in vitro studies suggest that HDACs may be novel pharmacological targets in immune-mediated islet beta-cell destruction. However, the role of specific HDAC in islet beta-cell development and function remain unclear. Here, we generated a conditional islet beta-cells specific HDAC3 deletion mouse model to determine the consequences of HDAC3 depletion on islet beta-cell differentiation, maintenance and function. Islet morphology, insulin secretion, glucose tolerance, and multiple low-dose streptozotocin (STZ)-induced diabetes incidence were evaluated and compared between HDAC3 knockout and wild type littermate controls. Mice with beta-cell-specific HDAC3 deletion displayed decreased pancreatic insulin content, disrupted glucose-stimulated insulin secretion, with intermittent spontaneous diabetes and dramatically enhanced susceptibility to STZ-induced diabetes. Furthermore, islet beta-cell line, MIN6 cells with siRNA-mediated HDAC3 silence, showed decreased insulin gene transcription, which was mediated, at least partially, through the upregulation of suppressors of cytokine signaling 3 (SOCS3). These results indicate the critical role of HDAC3 in normal beta-cell differentiation, maintenance and function. |
