Liang Aihong, Zhang Wenmao, Wang Qian, Huang Lan'e, Zhang Jiaming, Ma Duo, Liu Ke, Li Shiyu, Chen Xi, Li Shan, Lei Xiaocan
Hunan Province Innovative Training Base for Medical Postgraduates, Hengyang Medical School, University of South China and Yueyang Women & Children's Medical Center, Hengyang, Yueyang, Hunan, China.
Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, Hunan, China.
Front Nutr. 2023 Jan 18;9:1019562. doi: 10.3389/fnut.2022.1019562. eCollection 2022.
Insulin resistance (IR) has a close relationship with the main clinical manifestations of patients with PCOS; hence, the research and development of new drugs to treat PCOS by improving IR is a desiderate task at present. Resveratrol (RES) possesses a variety of beneficial pharmacological functions, such as antioxidation, anti-inflammatory, regulating glucose, and lipid metabolism. However, whether RES could improve IR and the underlying mechanisms remained unclear in PCOS.
SD rats received a high-fat diet and letrozole for 30 days to establish the PCOS model and then intervened with RES for 30 days. The results demonstrated that RES played a protective role on the IR in PCOS rats, which significantly decreased the levels of blood glucose and serum insulin, up regulated the expression of IGF1R, and down regulated the expression of IGF1. , KGN cells were treated with insulin, RES, and AGK2, respectively. We found that a high dose of insulin (4μg/mL) significantly inhibited KGN cell viability, decreased the level of lactic acid, and increased the level of pyruvate, while RES (25μM) attenuated the growth-inhibitory effect, as well as increased the level of lactic acid and decreased the level of pyruvate after high levels of insulin treatment. Simultaneously, RES up regulated the expression level of the crucial rate-limiting enzymes relating to glycolytic pathways, such as LDHA, HK2, and PKM2. Furthermore, AGK2 remarkably inhibited the expression level of SIRT2, which was similar to the same negative effects processed by insulin. Meanwhile, RES overtly repaired the glycolysis process by reversing the levels of lactic acid and pyruvate, together with up regulating the expression level of LDHA, HK2, and PKM2, after AGK2 treatment.
RES could effectively improve insulin resistance and restore the glycolysis pathway by regulating SIRT2, which may contribute to attenuating the ovarian damage of PCOS rats and provide a potential treatment for patients with PCOS.
胰岛素抵抗（IR）与多囊卵巢综合征（PCOS）患者的主要临床表现密切相关；因此，研发通过改善IR来治疗PCOS的新药是目前迫切需要完成的任务。白藜芦醇（RES）具有多种有益的药理功能，如抗氧化、抗炎、调节糖脂代谢。然而，在PCOS中RES是否能改善IR及其潜在机制仍不清楚。
将SD大鼠给予高脂饮食和来曲唑30天以建立PCOS模型，然后用RES干预30天。结果表明，RES对PCOS大鼠的IR起保护作用，显著降低血糖和血清胰岛素水平，上调IGF1R的表达，并下调IGF1的表达。分别用胰岛素、RES和AGK2处理KGN细胞。我们发现高剂量胰岛素（4μg/mL）显著抑制KGN细胞活力，降低乳酸水平，升高丙酮酸水平，而RES（25μM）减弱了生长抑制作用，并且在高剂量胰岛素处理后提高了乳酸水平并降低了丙酮酸水平。同时，RES上调了糖酵解途径相关关键限速酶的表达水平，如LDHA、HK2和PKM2。此外，AGK2显著抑制SIRT2的表达水平，这与胰岛素处理产生的负面影响相似。同时，在AGK2处理后，RES通过逆转乳酸和丙酮酸水平以及上调LDHA、HK2和PKM2的表达水平明显修复了糖酵解过程。
RES可通过调节SIRT2有效改善胰岛素抵抗并恢复糖酵解途径，这可能有助于减轻PCOS大鼠的卵巢损伤，并为PCOS患者提供一种潜在的治疗方法。
