Liu Haikun, Guo Dongsheng, Ruzi Aynisahan, Chen Yan, Pan Tingcai, Yang Fan, Li Jialiang, Xu Kecheng, Zhou Tiancheng, Qin Dajiang, Li Yin-Xiong
Institute of Public Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
School of Life Sciences, Anhui University, Hefei, China.
PLoS One. 2017 Jun 8;12(6):e0179353. doi: 10.1371/journal.pone.0179353. eCollection 2017.
Human induced pluripotent stem cells (hiPSCs) may provide potential resource for regenerative medicine research, including generation of insulin-producing cells for diabetes research and insulin production. Testosterone (T) is an androgen hormone which promotes protein synthesis and improves the management of type 2 diabetes in clinical studies. Concurrently, co-existed hyperandrogenism and hyperinsulinism is frequently observed in polycystic ovary syndrome, congenital adrenal hyperplasia and some of Wermer's syndrome. However, the relationship among androgens, insulin and the differentiation of pancreatic β cells is still not fully clear. Here we find that T improves the differentiation efficiency of insulin-producing cells from hiPSCs. The addition of T into routine differentiation formula for pancreatic β cells increases the differentiation efficiency from 12% to 35%. The administration of T promotes the expression of key genes associated with β cells differentiation including NGN3, NEUROD1 and INS. This finding benefits the ongoing process to optimize the differentiation protocol of pancreatic β cells from hiPSCs, and provides some degree of understanding the clinical management of T for type 2 diabetes.
人诱导多能干细胞(hiPSCs)可能为再生医学研究提供潜在资源,包括用于糖尿病研究的胰岛素生成细胞的生成及胰岛素生产。睾酮(T)是一种雄激素,在临床研究中可促进蛋白质合成并改善2型糖尿病的治疗。同时,多囊卵巢综合征、先天性肾上腺皮质增生症以及部分韦默综合征中常出现雄激素过多和胰岛素过多并存的情况。然而,雄激素、胰岛素与胰腺β细胞分化之间的关系仍不完全清楚。在此我们发现,睾酮可提高hiPSCs来源的胰岛素生成细胞的分化效率。在胰腺β细胞的常规分化培养基中添加睾酮可使分化效率从12%提高到35%。睾酮的施用促进了与β细胞分化相关的关键基因的表达,包括NGN3、NEUROD1和INS。这一发现有助于正在进行的优化hiPSCs来源的胰腺β细胞分化方案的进程,并为理解睾酮对2型糖尿病的临床治疗提供了一定程度的帮助。