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

## TL;DR

Kisspeptin helps reduce insulin resistance in PCOS by improving the PI3K/AKT/GLUT4 pathway and mitochondrial function in ovarian cells.

## Contribution

This study reveals a novel mechanism by which kisspeptin alleviates PCOS-related insulin resistance through specific signaling and mitochondrial pathways.

## Key findings

- Kisspeptin activates the PI3K/AKT pathway, increasing GLUT4 expression in granulosa cells.
- Kisspeptin reduces ROS levels and enhances mitochondrial membrane potential in vitro.
- The study identifies kisspeptin as a potential therapeutic target for PCOS-related insulin resistance.

## Abstract

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.

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.

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.

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.