{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:12:26Z","timestamp":1791911546352,"version":"4.3.4"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Weifang Health Commission","award":["WFWSJK-2023-005"],"award-info":[{"award-number":["WFWSJK-2023-005"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Insulin resistance (IR) is commonly observed in patients with polycystic ovary syndrome (PCOS), affecting 44% to 70% of these individuals. Kisspeptin is a key regulatory factor in energy balance and reproduction, and it may alleviate PCOS-related symptoms by improving insulin resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, a PCOS-IR mouse model was established using dehydroepiandrosterone (DHEA) and a high-fat diet. The expression of kisspeptin, PI3K, phosphorylated PI3K (p-PI3K), AKT, phosphorylated AKT (p-AKT), and glucose transporter 4 (GLUT4) was measured by immunofluorescence staining, quantitative PCR, and Western blotting. Flow cytometry was used to evaluate mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In granulosa cells from PCOS-IR mice, kisspeptin upregulated GLUT4 expression by activating the PI3K\/AKT signaling pathway. In vitro experiments showed that kisspeptin significantly reduced ROS levels, enhanced MMP, and improved mitochondrial function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Kisspeptin improves insulin resistance through the PI3K\/AKT\/GLUT4 signaling pathway and exerts its effects in vitro in granulosa cells. by protecting mitochondrial function. This study provides potential biomarkers and therapeutic targets for the treatment of PCOS-IR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0342158","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:38:52Z","timestamp":1770057532000},"page":"e0342158","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Kisspeptin improves local ovarian insulin resistance in PCOS by modulating the PI3K\/AKT\/GLUT4 signaling pathway"],"prefix":"10.1371","volume":"21","author":[{"given":"Na","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3999-1940","authenticated-orcid":true,"given":"Huagang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"issue":"3","key":"pone.0342158.ref001","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1001\/jama.2021.23769","article-title":"Diagnosis and Treatment of Polycystic Ovary Syndrome","volume":"327","author":"HG Huddleston","year":"2022","journal-title":"JAMA"},{"issue":"2","key":"pone.0342158.ref002","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23020583","article-title":"Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing","volume":"23","author":"HM Sadeghi","year":"2022","journal-title":"Int J Mol Sci"},{"key":"pone.0342158.ref003","doi-asserted-by":"crossref","first-page":"113201","DOI":"10.1016\/j.ecoenv.2022.113201","article-title":"Bisphenol F suppresses insulin-stimulated glucose metabolism in adipocytes by inhibiting IRS-1\/PI3K\/AKT pathway","volume":"231","author":"H Chen","year":"2022","journal-title":"Ecotoxicol Environ Saf"},{"key":"pone.0342158.ref004","doi-asserted-by":"crossref","first-page":"104544","DOI":"10.1016\/j.yrtph.2019.104544","article-title":"Berberine decreases insulin resistance in a PCOS rats by improving GLUT4: Dual regulation of the PI3K\/AKT and MAPK pathways","volume":"110","author":"N Zhang","year":"2020","journal-title":"Regul Toxicol Pharmacol"},{"issue":"11","key":"pone.0342158.ref005","article-title":"Corrigendum to: \u201cAdipocyte Insulin Resistance in PCOS: Relationship With GLUT-4 Expression and Whole-Body Glucose Disposal and \u03b2-Cell Function\u201d","volume":"105","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"pone.0342158.ref006","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.18632\/aging.202421","article-title":"LNK promotes granulosa cell apoptosis in PCOS via negatively regulating insulin-stimulated AKT-FOXO3 pathway","volume":"13","author":"M Tan","year":"2021","journal-title":"Aging (Albany NY)"},{"issue":"7","key":"pone.0342158.ref007","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/iub.1293","article-title":"Tissue-specific insulin signaling in the regulation of metabolism and aging","volume":"66","author":"J Zhang","year":"2014","journal-title":"IUBMB Life"},{"issue":"11","key":"pone.0342158.ref008","article-title":"Mechanisms of and potential medications for oxidative stress in ovarian granulosa cells: A review","volume":"24","author":"S Liu","year":"2023","journal-title":"Int J Mol Sci"},{"key":"pone.0342158.ref009","doi-asserted-by":"crossref","first-page":"154556","DOI":"10.1016\/j.phymed.2022.154556","article-title":"Chinese herbal medicine alleviates the pathogenesis of polycystic ovary syndrome by improving oxidative stress and glucose metabolism via mitochondrial Sirtuin 3 signaling","volume":"109","author":"Q Zhang","year":"2023","journal-title":"Phytomedicine"},{"key":"pone.0342158.ref010","doi-asserted-by":"crossref","first-page":"925206","DOI":"10.3389\/fendo.2022.925206","article-title":"The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction","volume":"13","author":"Q Xie","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"pone.0342158.ref011","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.theriogenology.2021.11.017","article-title":"Expression of kisspeptin and its receptor in different functional classes of ovarian follicle in the buffalo (Bubalus bubalis)","volume":"179","author":"TR Rajin","year":"2022","journal-title":"Theriogenology"},{"issue":"6","key":"pone.0342158.ref012","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqad077","article-title":"Deletion of Androgen Receptors From Kisspeptin Neurons Prevents PCOS Features in a Letrozole Mouse Model","volume":"164","author":"C Decourt","year":"2023","journal-title":"Endocrinology"},{"issue":"4","key":"pone.0342158.ref013","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1007\/s11845-021-02733-w","article-title":"Kisspeptin levels in relation to sex hormone profile among PCOS patients","volume":"191","author":"E Zarei","year":"2022","journal-title":"Ir J Med 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Zhang","year":"2022","journal-title":"Free Radic Biol Med"},{"issue":"2","key":"pone.0342158.ref017","article-title":"Effects of Berberine on glucolipid metabolism among dehydroepiandrosterone-induced rats of polycystic ovary syndrome with insulin-resistance","volume":"10","author":"L Li","year":"2024","journal-title":"Heliyon"},{"key":"pone.0342158.ref018","doi-asserted-by":"crossref","first-page":"1091147","DOI":"10.3389\/fendo.2022.1091147","article-title":"Insulin resistance, autophagy and apoptosis in patients with polycystic ovary syndrome: Association with PI3K signaling pathway","volume":"13","author":"C Tong","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"pone.0342158.ref019","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s11033-025-10553-9","article-title":"Exploring the role of Myo-inositol in alleviating insulin resistance in polycystic ovary syndrome through the AMPK\/GLUT4 pathway","volume":"52","author":"G Song","year":"2025","journal-title":"Mol Biol Rep"},{"issue":"3","key":"pone.0342158.ref020","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26031172","article-title":"A comprehensive review of the contribution of mitochondrial DNA mutations and dysfunction in polycystic ovary syndrome, supported by secondary database analysis","volume":"26","author":"H Kobayashi","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"12","key":"pone.0342158.ref021","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23126611","article-title":"The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review","volume":"23","author":"M Szyde\u0142ko-Gorzkowicz","year":"2022","journal-title":"Int J Mol Sci"},{"key":"pone.0342158.ref022","doi-asserted-by":"crossref","first-page":"116154","DOI":"10.1016\/j.envpol.2020.116154","article-title":"Subacute cadmium exposure disrupts the hypothalamic-pituitary-gonadal axis, leading to polycystic ovarian syndrome and premature ovarian failure features in female rats","volume":"269","author":"CS da Costa","year":"2021","journal-title":"Environ Pollut"},{"issue":"3","key":"pone.0342158.ref023","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s11011-025-01573-2","article-title":"Probiotics ameliorates hypothalamic amenorrhea in a rat model of PCOS","volume":"40","author":"SE Areloegbe","year":"2025","journal-title":"Metab Brain Dis"},{"issue":"4","key":"pone.0342158.ref024","doi-asserted-by":"crossref","first-page":"101793","DOI":"10.1016\/j.ando.2025.101793","article-title":"Kisspeptin system-physiology and clinical perspectives","volume":"86","author":"N Stoynev","year":"2025","journal-title":"Ann Endocrinol (Paris)"},{"issue":"2","key":"pone.0342158.ref025","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s43032-020-00437-7","article-title":"Kisspeptins and Glucose Homeostasis in Pregnancy: Implications for Gestational Diabetes Mellitus-a Review Article","volume":"29","author":"E 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