Hunan Province Joint Training Base for Top-notch Innovative Talents of Graduate Students, School of Basic Medical Sciences, Hengyang Medical School, University of South China and Hengyang Women & Children's Medical Center, Hengyang 421001, China.
Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Department of Obstetrics and Gynecology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China.
Int J Biol Macromol. 2024 Oct;278(Pt 2):134780. doi: 10.1016/j.ijbiomac.2024.134780. Epub 2024 Aug 16.
Insulin resistance (IR) is one of the major complications of polycystic ovary syndrome (PCOS). This study aimed to investigate the effects and the molecular regulatory mechanism by which Dendrobium nobile-derived polysaccharides (DNP) improve IR in rats with letrozole and high-fat-diet induced PCOS. In vivo, DNP (200 mg/kg/d) administration not only reduced body weight, blood glucose, and insulin levels in PCOS rats, but also improve the disrupted estrous cycle. In addition, DNP treatment reduced atretic and cystic follicles and enhanced granulosa cell layer thickness, thereby restoring follicle development. In vitro, DNP treatment (100 μM) increased lactate levels and decreased pyruvate levels in insulin-treated (8 μg/mL) KGN cells. Additionally, DNP also decreased the expression of IGF1 and increased that of IGF1R, SIRT2, LDHA, PKM2 and HK2 both in vivo and in vitro. Also, SIRT2 expression was specifically inhibited by AGK2, while DNP significantly improved IR and glycolysis by reversing the effect of AGK2 treatment on lactate and pyruvate production, upregulating the expression levels of IGF1R, LDHA, HK2, and PKM2 and downregulating the expression level of IGF1. The results indicate that DNP can effectively improve IR and restore glycolytic pathway by activating SIRT2, which may provide a potential therapeutic approach for PCOS patients.
胰岛素抵抗（IR）是多囊卵巢综合征（PCOS）的主要并发症之一。本研究旨在探讨铁皮石斛多糖（DNP）改善来曲唑和高脂饮食诱导的 PCOS 大鼠 IR 的作用及其分子调控机制。在体内，DNP（200mg/kg/d）给药不仅降低了 PCOS 大鼠的体重、血糖和胰岛素水平，还改善了紊乱的动情周期。此外，DNP 治疗减少了闭锁和囊性卵泡，并增强了颗粒细胞层厚度，从而恢复了卵泡发育。在体外，DNP 处理（100μM）增加了胰岛素处理（8μg/mL）KGN 细胞中的乳酸水平，降低了丙酮酸水平。此外，DNP 还降低了 IGF1 的表达，增加了 IGF1R、SIRT2、LDHA、PKM2 和 HK2 的表达，无论是在体内还是体外。此外，SIRT2 的表达被 AGK2 特异性抑制，而 DNP 通过逆转 AGK2 处理对乳酸和丙酮酸产生的影响、上调 IGF1R、LDHA、HK2 和 PKM2 的表达水平以及下调 IGF1 的表达水平，显著改善了 IR 和糖酵解。结果表明，DNP 可以通过激活 SIRT2 有效改善 IR 并恢复糖酵解途径，这可能为 PCOS 患者提供一种潜在的治疗方法。
