Kisspeptin improves local ovarian insulin resistance in PCOS by modulating the PI3K/AKT/GLUT4 signaling pathway.

Abstract

BACKGROUND: Insulin resistance (IR) is commonly observed in patients with polycystic ovary syndrome (PCOS), affecting 44% to 70% of these individuals. Kisspeptin is a key regulatory factor in energy balance and reproduction, and it may alleviate PCOS-related symptoms by improving insulin resistance. METHODS: In this study, a PCOS-IR mouse model was established using dehydroepiandrosterone (DHEA) and a high-fat diet. The expression of kisspeptin, PI3K, phosphorylated PI3K (p-PI3K), AKT, phosphorylated AKT (p-AKT), and glucose transporter 4 (GLUT4) was measured by immunofluorescence staining, quantitative PCR, and Western blotting. Flow cytometry was used to evaluate mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels. RESULTS: In granulosa cells from PCOS-IR mice, kisspeptin upregulated GLUT4 expression by activating the PI3K/AKT signaling pathway. In vitro experiments showed that kisspeptin significantly reduced ROS levels, enhanced MMP, and improved mitochondrial function. CONCLUSION: Kisspeptin improves insulin resistance through the PI3K/AKT/GLUT4 signaling pathway and exerts its effects in vitro in granulosa cells. by protecting mitochondrial function. This study provides potential biomarkers and therapeutic targets for the treatment of PCOS-IR.