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

Insulin plays an important role in regulation of lipid and glucose metabolism. Retinoic acid receptor-related orphan receptor alpha (ROR alpha) modulates physiopathological processes such as dyslipidemia and diabetes. In this study, we found overexpression of ROR alpha in INS1 cells resulted in increased expression and secretion of insulin. Suppression of endogenous ROR alpha caused a decrease of insulin expression. Luciferase and electrophoretic mobility shift assay (EMSA) assays demonstrated that ROR alpha activated insulin transcription via direct binding to its promoter. ROR alpha 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 ROR alpha agonist SR1078. These findings identify ROR alpha as a transcriptional activator of insulin and suggest novel therapeutic opportunities for management of the disease. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.