Cited by 37Ovarian function and disordersReproductive Biology and FertilityCircadian rhythm and melatonin

Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome

Guo, Rui, Zheng, Hong, Li, Qiuying, Qiu, Xun, Zhang, Jian, Cheng, Zhaofang·2022·Reproductive Biology

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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Crossref · 10.1016/j.repbio.2021.100594

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  1. Heo, 2018, Melatonin improves insulin resistance and hepatic steatosis through attenuation of alpha-2-HS-glycoprotein, J Pineal Res, 65, 10.1111/jpi.12493 · DOI

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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
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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