| First Author | Miyazaki S | Year | 2010 |
| Journal | Diabetes | Volume | 59 |
| Issue | 11 | Pages | 2854-61 |
| PubMed ID | 20798333 | Mgi Jnum | J:169730 |
| Mgi Id | MGI:4941704 | Doi | 10.2337/db09-1897 |
| Citation | Miyazaki S, et al. (2010) Nuclear hormone retinoid X receptor (RXR) negatively regulates the glucose-stimulated insulin secretion of pancreatic ss-cells. Diabetes 59(11):2854-61 |
| abstractText | OBJECTIVE: Retinoid X receptors (RXRs) are members of the nuclear hormone receptor superfamily and are thought to be key regulators in differentiation, cellular growth, and gene expression. Although several experiments using pancreatic beta-cell lines have shown that the ligands of nuclear hormone receptors modulate insulin secretion, it is not clear whether RXRs have any role in insulin secretion. RESEARCH DESIGN AND METHODS: To elucidate the function of RXRs in pancreatic beta-cells, we generated a double-transgenic mouse in which a dominant-negative form of RXRbeta was inducibly expressed in pancreatic beta-cells using the Tet-On system. We also established a pancreatic beta-cell line from an insulinoma caused by the beta-cell-specific expression of simian virus 40 T antigen in the above transgenic mouse. RESULTS: In the transgenic mouse, expression of the dominant-negative RXR enhanced the insulin secretion with high glucose stimulation. In the pancreatic beta-cell line, the suppression of RXRs also enhanced glucose-stimulated insulin secretion at a high glucose concentration, while 9-cis-retinoic acid, an RXR agonist, repressed it. High-density oligonucleotide microarray analysis showed that expression of the dominant-negative RXR affected the expression levels of a number of genes, some of which have been implicated in the function and/or differentiation of beta-cells. CONCLUSIONS: These results suggest that endogenous RXR negatively regulates the glucose-stimulated insulin secretion. Given these findings, we propose that the modulation of endogenous RXR in beta-cells may be a new therapeutic approach for improving impaired insulin secretion in type 2 diabetes. |
