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Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: A Human and Rat Model-Based Study.
Endocrinology. 2021 08 01; 162(8)E

Abstract

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism and insulin resistance (IR); however, the pathogenesis of local ovarian IR in PCOS remains largely unclear. Humanin, a mitochondria-derived peptide, has been reported to be associated with IR. Our previous study confirmed that humanin is expressed in multiple cell types in the ovary and is present in follicular fluid. However, it remains unknown whether humanin participates in the pathogenesis of local ovarian IR or whether humanin supplementation can improve IR in PCOS patients. In this study, we compared humanin concentrations in follicular fluid from PCOS patients with and without IR. We further investigated the effect of humanin analogue (HNG) supplementation on IR in a rat model of dehydroepiandrosterone-induced PCOS. Humanin concentrations in the follicular fluid were found to be significantly lower in PCOS patients with IR than in those without IR. HNG supplementation attenuated both the increases in the levels of fasting plasma glucose and fasting insulin in rats with PCOS and the decreases in phosphorylation of IRS1, PI3K, AKT, and GLUT4 proteins in the granulosa cells of these rats. Combined supplementation with HNG and insulin significantly improved glucose consumption in normal and humanin-siRNA-transfected COV434 cells. In conclusion, downregulated humanin in the ovaries may be involved in the pathogenesis of IR in PCOS, and exogenous supplementation with HNG improved local ovarian IR through modulation of the IRS1/PI3K/Akt signaling pathway in a rat model. This finding supports the potential future use of HNG as a therapeutic drug for PCOS.

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Authors+Show Affiliations

Wang Y
Reproductive Health Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zeng Z
Department of General Medicine, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Zhao S
Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Tang L
Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Yan J
Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Li N
Reproductive Health Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zou L
Reproductive Health Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Fan X
Reproductive Health Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Xu C
Reproductive Health Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Huang J
Reproductive Health Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Xia W
Reproductive Health Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Reproductive Medicine Centre, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhu C
Reproductive Health Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Reproductive Medicine Centre, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Rao M
Department of Reproduction and Genetics, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.

MeSH

AdultAnimalsCase-Control StudiesCell LineDisease Models, AnimalDrug Evaluation, PreclinicalFemaleFollicular FluidGlucose Transporter Type 4Granulosa CellsHumansInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsPhosphatidylinositol 3-KinasesPolycystic Ovary SyndromePrimary Cell CultureProto-Oncogene Proteins c-aktRats, Sprague-DawleySignal TransductionYoung Adult

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33693742

Citation

Wang, Yingying, et al. "Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: a Human and Rat Model-Based Study." Endocrinology, vol. 162, no. 8, 2021.
Wang Y, Zeng Z, Zhao S, et al. Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: A Human and Rat Model-Based Study. Endocrinology. 2021;162(8).
Wang, Y., Zeng, Z., Zhao, S., Tang, L., Yan, J., Li, N., Zou, L., Fan, X., Xu, C., Huang, J., Xia, W., Zhu, C., & Rao, M. (2021). Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: A Human and Rat Model-Based Study. Endocrinology, 162(8). https://doi.org/10.1210/endocr/bqab056
Wang Y, et al. Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: a Human and Rat Model-Based Study. Endocrinology. 2021 08 1;162(8) PubMed PMID: 33693742.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: A Human and Rat Model-Based Study. AU - Wang,Yingying, AU - Zeng,Zhengyan, AU - Zhao,Shuhua, AU - Tang,Li, AU - Yan,Jin, AU - Li,Nianyu, AU - Zou,Liping, AU - Fan,Xiaorong, AU - Xu,Chengcheng, AU - Huang,Jin, AU - Xia,Wei, AU - Zhu,Changhong, AU - Rao,Meng, PY - 2020/11/04/received PY - 2021/3/12/pubmed PY - 2021/10/21/medline PY - 2021/3/11/entrez KW - PCOS KW - granulosa cell KW - humanin KW - insulin resistance JF - Endocrinology JO - Endocrinology VL - 162 IS - 8 N2 - Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism and insulin resistance (IR); however, the pathogenesis of local ovarian IR in PCOS remains largely unclear. Humanin, a mitochondria-derived peptide, has been reported to be associated with IR. Our previous study confirmed that humanin is expressed in multiple cell types in the ovary and is present in follicular fluid. However, it remains unknown whether humanin participates in the pathogenesis of local ovarian IR or whether humanin supplementation can improve IR in PCOS patients. In this study, we compared humanin concentrations in follicular fluid from PCOS patients with and without IR. We further investigated the effect of humanin analogue (HNG) supplementation on IR in a rat model of dehydroepiandrosterone-induced PCOS. Humanin concentrations in the follicular fluid were found to be significantly lower in PCOS patients with IR than in those without IR. HNG supplementation attenuated both the increases in the levels of fasting plasma glucose and fasting insulin in rats with PCOS and the decreases in phosphorylation of IRS1, PI3K, AKT, and GLUT4 proteins in the granulosa cells of these rats. Combined supplementation with HNG and insulin significantly improved glucose consumption in normal and humanin-siRNA-transfected COV434 cells. In conclusion, downregulated humanin in the ovaries may be involved in the pathogenesis of IR in PCOS, and exogenous supplementation with HNG improved local ovarian IR through modulation of the IRS1/PI3K/Akt signaling pathway in a rat model. This finding supports the potential future use of HNG as a therapeutic drug for PCOS. SN - 1945-7170 UR - https://www.unboundmedicine.com/medline/citation/33693742/Humanin_Alleviates_Insulin_Resistance_in_Polycystic_Ovary_Syndrome:_A_Human_and_Rat_Model_Based_Study_ DB - PRIME DP - Unbound Medicine ER -