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Identification of insulin as a novel retinoic acid receptor‐related orphan receptor α target gene
Author(s) -
Kuang Jiangying,
Hou Xiaoming,
Zhang Jinlong,
Chen Yulong,
Su Zhiguang
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.02.029
Subject(s) - orphan receptor , insulin , retinoic acid receptor , retinoic acid , nuclear receptor , insulin receptor , insulin receptor substrate , chemistry , electrophoretic mobility shift assay , transcription factor , endocrinology , medicine , biology , biochemistry , insulin resistance , gene
Insulin plays an important role in regulation of lipid and glucose metabolism. Retinoic acid receptor‐related orphan receptor α (RORα) modulates physiopathological processes such as dyslipidemia and diabetes. In this study, we found overexpression of RORα in INS1 cells resulted in increased expression and secretion of insulin. Suppression of endogenous RORα caused a decrease of insulin expression. Luciferase and electrophoretic mobility shift assay (EMSA) assays demonstrated that RORα activated insulin transcription via direct binding to its promoter. RORα 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 RORα agonist SR1078. These findings identify RORα as a transcriptional activator of insulin and suggest novel therapeutic opportunities for management of the disease.