title: Identification of insulin as a novel retinoic acid receptor-related orphan receptor α target gene.
abstract: 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.
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jiangying
authors.initials: J
authors.lastname: Kuang
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hou
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. Electronic address: zhiguang_su@hotmail.com.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Su
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D016384:Consensus Sequence; D015870:Gene Expression; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D000078790:Insulin Secretion; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D020218:Response Elements; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D051473:Maf Transcription Factors, Large; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D015534:Trans-Activators; C485160:Mafa protein, mouse; C501008:Neurod1 protein, mouse; C539739:Rora protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein
keywords: Gene transcription; Insulin; Promoter; Retinoic acid receptor-related orphan receptor α