Nesfatin-1 regulates the phenotype transition of cavernous smooth muscle cells by activating PI3K/AKT/mTOR signaling pathway to improve diabetic erectile dysfunction

作者：Keming Chen, Bincheng Huang, Jiajing Feng, Shuzhe Fan, Zhengxing Hu, Shuai Ren, Haifu Tian, A.L.-QAISIMOHAMMED Abdulkarem, Xuehao Wang, Yunshang Tuo, Xiaoxia Liang, Haibo Xie, Rui He, Guangyong Li · 发表于：Heliyon · 年份：2024 · DOI：10.1016/j.heliyon.2024.e32524 · 被引用次数：8 · 研究领域：Sexual function and dysfunction studies、Adipokines, Inflammation, and Metabolic Diseases、Regulation of Appetite and Obesity

Objective This study aims to explore the impact of Nesfatin-1 on type 2 diabetic erectile dysfunction (T2DMED) and its underlying mechanism in regulating the phenotypic switching of corpus cavernosum smooth muscle cells (CCSMCs). Methods Twenty-four 4-week-old male C57 wild-type mice were randomly assigned to the control group, model group, and Nesfatin-1 treatment group. Monitoring included body weight, blood glucose levels, and penile cavernous pressure (ICP). Histochemistry and Western blot analyses were conducted to assess the expressions of α-SMA, OPN, and factors related to the PI3K/AKT/mTOR signaling pathway. CCSMCs were categorized into the control group, high glucose and high oleic acid group (GO group), Nesfatin-1 treatment group (GO + N group), sildenafil positive control group (GO + S group), and PI3K inhibitor group (GO + N + E group). Changes in phenotypic markers, cell morphology, and the PI3K/AKT/mTOR signaling pathway were observed in each group. Results (1) Nesfatin-1 significantly ameliorated the body size, body weight, blood glucose, glucose tolerance, and insulin resistance in T2DMED mice. (2) Following Nesfatin-1 treatment, the ICP/MSBP ratio and the peak of the ICP curve demonstrated a significant increase. (3) Nesfatin-1 significantly enhanced smooth muscle and reduced collagen fibers in the corpus cavernosum. (4) Nesfatin-1 notably increased α-SMA expression and decreased OPN expression in CCSMCs. (5) Nesfatin-1 elevated PI3K, p -AKT/AKT, and p -mTOR/...