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Publication : Identification of insulin as a novel retinoic acid receptor-related orphan receptor α target gene.

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.
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