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Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome.
Reprod Biol. 2022 Mar; 22(1):100594.RB

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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Publisher Full Text (DOI)

Authors+Show Affiliations

Guo R
Reproductive Medicine Center, Shandong Maternal and Child Health Care Center, NO. 238, East Jingshi Road, Jinan 250014, Shandong, China.
Zheng H
Department of Reproductive Medicine, Dezhou People's Hospital, NO. 1166, Dongfanghong West Road, Dezhou 253014, Shandong, China.
Li Q
Department of Radiology, Zhangqiu People's Hospital, NO. 1920, Huiquan Road, Jinan 250200, Shandong, China.
Qiu X
Department of Radiology, Zhangqiu People's Hospital, NO. 1920, Huiquan Road, Jinan 250200, Shandong, China.
Zhang J
Department of Radiology, Zhangqiu People's Hospital, NO. 1920, Huiquan Road, Jinan 250200, Shandong, China.
Cheng Z
Department of Radiology, Zhangqiu People's Hospital, NO. 1920, Huiquan Road, Jinan 250200, Shandong, China; Department of Obstetrics and Gynecology, Zhangqiu People's Hospital, NO. 1920, Huiquan Road, Jinan 250200, Shandong, China. Electronic address: chengzhaofang1106@163.com.

MeSH

FemaleGranulosa CellsHumansInsulin ResistanceMelatoninPhosphatidylinositol 3-KinasesPolycystic Ovary SyndromeProto-Oncogene Proteins c-aktSignal Transduction

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34953312

Citation

Guo, Rui, et al. "Melatonin Alleviates Insulin Resistance Through the PI3K/AKT Signaling Pathway in Ovary Granulosa Cells of Polycystic Ovary Syndrome." Reproductive Biology, vol. 22, no. 1, 2022, p. 100594.
Guo R, Zheng H, Li Q, et al. Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome. Reprod Biol. 2022;22(1):100594.
Guo, R., Zheng, H., Li, Q., Qiu, X., Zhang, J., & Cheng, Z. (2022). Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome. Reproductive Biology, 22(1), 100594. https://doi.org/10.1016/j.repbio.2021.100594
Guo R, et al. Melatonin Alleviates Insulin Resistance Through the PI3K/AKT Signaling Pathway in Ovary Granulosa Cells of Polycystic Ovary Syndrome. Reprod Biol. 2022;22(1):100594. PubMed PMID: 34953312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome. AU - Guo,Rui, AU - Zheng,Hong, AU - Li,Qiuying, AU - Qiu,Xun, AU - Zhang,Jian, AU - Cheng,Zhaofang, Y1 - 2021/12/22/ PY - 2021/09/28/received PY - 2021/12/03/revised PY - 2021/12/05/accepted PY - 2021/12/26/pubmed PY - 2022/3/9/medline PY - 2021/12/25/entrez KW - Granulosa cells KW - Insulin resistance KW - Melatonin KW - Palmitic acid KW - Polycystic ovary syndrome SP - 100594 EP - 100594 JF - Reproductive biology JO - Reprod Biol VL - 22 IS - 1 N2 - 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. SN - 2300-732X UR - https://www.unboundmedicine.com/medline/citation/34953312/Melatonin_alleviates_insulin_resistance_through_the_PI3K/AKT_signaling_pathway_in_ovary_granulosa_cells_of_polycystic_ovary_syndrome_ DB - PRIME DP - Unbound Medicine ER -