Department of Endocrinology, Henan Provincial People's Hospital , Zhengzhou , Henan , China.
Department of Neurosurgery, Henan Provincial People's Hospital , Zhengzhou , Henan , China.
Cell Cycle. 2019 Oct;18(19):2538-2549. doi: 10.1080/15384101.2019.1652036. Epub 2019 Aug 12.
Insulin resistance (IR) is prevalent in women with polycystic ovary syndrome (PCOS). Improvement in insulin sensitivity remains one of the most effective treatment strategies for women with PCOS. This study aims to investigate the efficacy and potential mechanism of the combination therapy with metformin (DMBG) and sitagliptin (TECOS) in PCOS. To address this, insulin was used to treat rat ovarian granulosa cells to establish the cellular PCOS model. Insulin and human chorionic gonadotropin (HCG) were subcutaneously injected into SD rats to establish a rat model of hyperandrogenism with pathogenesis similar to PCOS. Our results showed that co-treatment with TECOS and DMBG attenuated the induced apoptosis and insulin resistance (IR) in PCOS model cells, and improved reproductive hormone disorders, ovarian polycystic changes, and IR of PCOS rats. Mechanistically, upregulation of H19 by H19-expressing lentiviruses enhanced efficacy of combination therapy. Furthermore, co-treatment with TECOS and DMBG induced H19 expression via suppressing the PI3K/AKT-DNMT1 pathway. Collectively, these findings demonstrate that combination treatment with TECOS and DMBG ameliorates PCOS with IR, at least partially, through upregulation of lncRNA H19.
胰岛素抵抗（IR）在多囊卵巢综合征（PCOS）妇女中很常见。提高胰岛素敏感性仍然是治疗 PCOS 妇女的最有效策略之一。本研究旨在探讨二甲双胍（DMBG）和西他列汀（TECOS）联合治疗 PCOS 的疗效和潜在机制。为此，我们使用胰岛素处理大鼠卵巢颗粒细胞建立了细胞 PCOS 模型。胰岛素和人绒毛膜促性腺激素（HCG）皮下注射 SD 大鼠，建立与 PCOS 发病机制相似的高雄激素血症大鼠模型。我们的结果表明，TECOS 和 DMBG 的联合治疗可减轻 PCOS 模型细胞的诱导性凋亡和胰岛素抵抗（IR），改善生殖激素紊乱、卵巢多囊性改变和 PCOS 大鼠的 IR。从机制上讲，H19 表达慢病毒上调 H19 增强了联合治疗的效果。此外，TECOS 和 DMBG 的联合治疗通过抑制 PI3K/AKT-DNMT1 通路诱导 H19 表达。总之，这些发现表明，TECOS 和 DMBG 的联合治疗通过上调 lncRNA H19 改善了伴有 IR 的 PCOS。
