To systematically map specific molecular disturbances in insulin signaling and carbohydrate metabolism in PCOS and identify key gaps in current evidence.
Key Findings:
Insulin resistance is present in 75–95% of women with PCOS, independent of body mass index.
Key mechanisms of insulin resistance include defects in IRS/PI3K/AKT and MAPK signaling, impaired GLUT4 expression, mitochondrial dysfunction, chronic inflammation, and androgen receptor-mediated metabolic changes, with evidence primarily derived from granulosa cells and ovarian tissue, and limited human studies.
Interpretation:
The review highlights significant molecular mechanisms contributing to insulin resistance in PCOS and emphasizes the need for more high-quality human research to validate these findings and their implications for clinical practice.
Limitations:
Limited evidence from human studies; many mechanisms supported mainly by rodent or cell line models, which may not fully translate to human physiology.
Heterogeneity in tissues examined and molecular pathways assessed across studies, complicating the synthesis of findings.
Conclusion:
Further longitudinal human research with comprehensive multi-omics is necessary to validate key mechanisms in ovarian and metabolic tissues related to insulin resistance in PCOS.
by Mikołaj Kisiała, Wiktoria Mazepa, Dominika Bauer, Patrycja Tabaka, Michał Gas, Aleksander Sowiński, Krzysztof Wolak, Albert Synal, Julia Gąsiorowska, Oliwia Sas, Wojciech Urbański, Oliwier Pioterek, Mateusz Mazurek, Zygmunt Domagała
