Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
FEBS Lett. 2014 Mar 18;588(6):1071-9. doi: 10.1016/j.febslet.2014.02.029. Epub 2014 Feb 25.
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.
胰岛素在调节脂质和葡萄糖代谢方面发挥着重要作用。维甲酸受体相关孤儿受体α（RORα）调节诸如血脂异常和糖尿病等生理病理过程。在这项研究中，我们发现 INS1 细胞中 RORα 的过表达导致胰岛素的表达和分泌增加。内源性 RORα 的抑制导致胰岛素表达减少。荧光素酶和电泳迁移率变动分析（EMSA）试验表明，RORα 通过直接结合其启动子激活胰岛素转录。还观察到 RORα 调节 BETA2 表达，BETA2 是胰岛素活性转录因子之一。体内分析表明，合成的 RORα 激动剂 SR1078 增加了胰岛素的转录。这些发现将 RORα 鉴定为胰岛素的转录激活剂，并为该疾病的治疗提供了新的治疗机会。
