First Author | Kuang J | Year | 2014 |
Journal | FEBS Lett | Volume | 588 |
Issue | 6 | Pages | 1071-9 |
PubMed ID | 24583012 | Mgi Jnum | J:208142 |
Mgi Id | MGI:5561164 | Doi | 10.1016/j.febslet.2014.02.029 |
Citation | Kuang J, et al. (2014) Identification of insulin as a novel retinoic acid receptor-related orphan receptor alpha target gene. FEBS Lett 588(6):1071-9 |
abstractText | Insulin plays an important role in regulation of lipid and glucose metabolism. Retinoic acid receptor-related orphan receptor alpha (RORalpha) modulates physiopathological processes such as dyslipidemia and diabetes. In this study, we found overexpression of RORalpha in INS1 cells resulted in increased expression and secretion of insulin. Suppression of endogenous RORalpha caused a decrease of insulin expression. Luciferase and electrophoretic mobility shift assay (EMSA) assays demonstrated that RORalpha activated insulin transcription via direct binding to its promoter. RORalpha was also observed to regulate BETA2 expression, which is one of the insulin active transfactors. In vivo analyses showed that the insulin transcription is increased by the synthetic RORalpha agonist SR1078. These findings identify RORalpha as a transcriptional activator of insulin and suggest novel therapeutic opportunities for management of the disease. |