Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine gynecological disorder. Insulin resistance (IR) is a major cause of PCOS. Melatonin, a critical endogenous hormone, has beneficial effects on the female reproductive system. This study aims to investigate the molecular effect of melatonin on IR in human ovarian granulosa cells (GCs). Hormone levels of the subjects were determined through clinical examination. The expression levels of insulin receptor substrate (IRS)-1 and glucose transporter (GLUT4) in GCs from PCOS patients and a human granulosa cell line (SVOG) were examined using qRT-PCR and western blot. The IR cell model was established by inducing SVOG cells with palmitic acid (PA). IR was detected in GCs of PCOS patients and SVOG by measuring glucose content and glucose uptake. Cell viability and apoptosis levels were detected by CCK-8 assay and flow cytometry. PI3K/Akt pathway expression in SVOG was assessed by western blot. PCOS patients had higher levels of luteinizing hormone (LH), testosterone, and LH/follicle-stimulating hormone. PA decreased cell viability, promoted apoptosis, and reduced glucose uptake in SVOG cells. IRS-1 and GLUT4 mRNA and protein expression was downregulated, and glucose uptake capacity was reduced in PCOS GCs and SVOG cells. Melatonin significantly upregulated IRS-1 and GLUT4 expression, downregulated p-IRS-1 (Ser307), and improved glucose uptake in PCOS patients' GCs and SVOG cells. PA decreased PI3K and Akt phosphorylation, whereas melatonin increased p-PI3K and p-Akt levels. Melatonin can reduce IR in GCs and PA-induced SVOG cells via the PI3K/Akt signaling pathway, providing more evidence for treating polycystic ovary syndrome.
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Reduced phosphorylation of the PI3K/Akt pathway is a hallmark of insulin resistance in PCOS patients.
“Reduced phosphorylation of the PI3K/Akt pathway is a hallmark of IR in PCOS patients10–12.”
From Efficacy and safety of GLP-1 receptor agonists on weight management and metabolic parameters in PCOS women: a meta-analysis of randomized controlled trials (2025) · cites this paper as [12]
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- Authors
- Guo, R., Zheng, H., Li, Q., Qiu, X., Zhang, J., & Cheng, Z.
- Affiliations
- Shandong Maternal and Child Health Hospital (CN)
- Zhangqiu City People's Hospital (CN)
- Corresponding author
- Cheng, Zhaofang
- Venue
- Reproductive Biology
- Publisher
- Elsevier BV
- Published
- 2022-03
- Volume
- 22
- Issue
- 1
- Pages
- 100594
- ISSN
- 1642-431X (ISSN-L)
- OpenAlex
- W4200119439
- Semantic Scholar
- f7b45d7a4e211f36253e547dfc979c275ab528b0
- Cited by
- 37
- References
- 46
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 6 · 2023: 9 · 2022: 5
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Reproductive Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- melatonin, polycystic ovary syndrome, insulin resistance, granulosa cells, PI3K/Akt signaling, IRS-1, GLUT4, glucose uptake, palmitic acid, apoptosis, luteinizing hormone, testosterone
- MeSH terms
- Female, Granulosa Cells, Humans, Insulin Resistance, Melatonin, Polycystic Ovary Syndrome, Signal Transduction, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt
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