{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:45:55Z","timestamp":1792532755052,"version":"4.5.0"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting women of reproductive age, characterized by oligo- or anovulation, hyperandrogenism, and polycystic ovarian morphology. Beyond its reproductive manifestations, PCOS is increasingly recognized as a complex endocrine\u2013metabolic disorder frequently associated with impaired carbohydrate metabolism and insulin resistance, often independent of body mass. Despite extensive research, the molecular mechanisms underlying insulin resistance across metabolic and reproductive tissues in PCOS remain incompletely characterized. This scoping review aimed to systematically map molecular disturbances in insulin signaling and carbohydrate metabolism in PCOS, explore associations between tissue-specific mechanisms, and identify key gaps in the current evidence. We included peer-reviewed original studies published in English between January 2018 and May 2025, retrieved from PubMed, Embase, and Web of Science, that investigated molecular or cellular pathways related to insulin resistance or glucose metabolism in PCOS. The available evidence predominantly addressed granulosa cells and ovarian tissue, with additional data from endometrium, liver, adipose tissue, skeletal muscle, pancreatic beta-cells, and systemic regulatory pathways. Recurrent mechanisms underlying insulin resistance in PCOS included post-receptor defects in IRS\/PI3K\/AKT and MAPK signaling, impaired GLUT4 expression and trafficking, mitochondrial and glycolytic dysfunction, chronic low-grade inflammation, androgen receptor\u2013mediated metabolic reprogramming, circadian rhythm disruption, and epigenetic or environmental modulators. Evidence from human studies remains limited, with many proposed molecular mechanisms being supported predominantly by rodent or cell line models. To translate this knowledge to clinical and therapeutic application, additional high-quality longitudinal human research with comprehensive multi-omics is necessary to validate key mechanisms in ovarian and metabolic tissues, especially those involving IRS\/PI3K\/AKT signaling, GLUT4 regulation, inflammation, and androgen-driven metabolic dysfunction.<\/jats:p>","DOI":"10.3389\/fendo.2026.1810805","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:47:31Z","timestamp":1776055651000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular mechanisms of insulin resistance and altered carbohydrate metabolism in PCOS: a scoping review"],"prefix":"10.3389","volume":"17","author":[{"given":"Miko\u0142aj","family":"Kisia\u0142a","sequence":"first","affiliation":[{"name":"Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiktoria","family":"Mazepa","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Bauer","sequence":"additional","affiliation":[{"name":"Clinical and Dissecting Anatomy Scientific Club, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Tabaka","sequence":"additional","affiliation":[{"name":"Clinical and Dissecting Anatomy Scientific Club, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Gas","sequence":"additional","affiliation":[{"name":"Clinical and Dissecting Anatomy Scientific Club, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Sowi\u0144ski","sequence":"additional","affiliation":[{"name":"Clinical and Dissecting Anatomy Scientific Club, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Wolak","sequence":"additional","affiliation":[{"name":"Clinical and Dissecting Anatomy Scientific Club, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Synal","sequence":"additional","affiliation":[{"name":"Clinical and Dissecting Anatomy Scientific Club, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"G\u0105siorowska","sequence":"additional","affiliation":[{"name":"Clinical and Dissecting Anatomy Scientific Club, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliwia","family":"Sas","sequence":"additional","affiliation":[{"name":"Clinical and Dissecting Anatomy Scientific Club, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Urba\u0144ski","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliwier","family":"Pioterek","sequence":"additional","affiliation":[{"name":"Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Mazurek","sequence":"additional","affiliation":[{"name":"Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zygmunt","family":"Domaga\u0142a","sequence":"additional","affiliation":[{"name":"Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-024-07607-x","article-title":"Global prevalence of polycystic ovary syndrome in women worldwide: A comprehensive systematic review and meta-analysis","volume":"310","author":"Salari","year":"2024","journal-title":"Arch Gynecol Obstet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des463","article-title":"Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp","volume":"28","author":"Stepto","year":"2013","journal-title":"Hum Reprod"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/ejendo\/lvad096","article-title":"Recommendations from the 2023 International Evidence-Based Guideline for the assessment and management of polycystic ovary syndrome","volume":"189","author":"Teede","year":"2023","journal-title":"Eur J Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2018.05.004","article-title":"Recommendations from the International Evidence-Based Guideline for the assessment and management of polycystic ovary syndrome","volume":"110","author":"Teede","year":"2018","journal-title":"Fertil Steril"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.11124\/jbies-20-00167","article-title":"Updated methodological guidance for the conduct of scoping reviews","volume":"18","author":"Peters","year":"2020","journal-title":"JBI Evid Synth"},{"key":"B6","first-page":"210","article-title":"Rayyan\u2014a web and mobile app for systematic reviews","volume-title":"Systematic reviews","author":"Ouzzani","year":"2016"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/cl2.1230","article-title":"Prisma2020: An R package and Shiny app for producing Prisma 2020-compliant flow diagrams, with interactivity for optimised digital transparency and open synthesis","volume":"18","author":"Haddaway","year":"2022","journal-title":"Campbell Syst Rev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/cells11182821","article-title":"Decreased expression of Sam68 is associated with insulin resistance in granulosa cells from PCOS patients","volume":"11","author":"Vilari\u00f1o-Garc\u00eda","year":"2022","journal-title":"Cells"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2018.01.008","article-title":"Differential insulin and steroidogenic signaling in insulin resistant and non-insulin resistant human luteinized granulosa cells-a study in PCOS patients","volume":"178","author":"Belani","year":"2018","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-018-1953-7","article-title":"Mif may participate in pathogenesis of polycystic ovary syndrome in rats through Mapk signalling pathway","volume":"38","author":"Zhou","year":"2018","journal-title":"Curr Med Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154749","article-title":"Addressing the role of 11\u03b2-hydroxysteroid dehydrogenase type 1 in the development of polycystic ovary syndrome and the putative therapeutic effects of its selective inhibition in a preclinical model","volume":"119","author":"Li","year":"2021","journal-title":"Metabolism"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac067","article-title":"At the crossroads of fertility and metabolism: The importance of Ampk-dependent signaling in female infertility associated with hyperandrogenism","volume":"37","author":"Froment","year":"2022","journal-title":"Hum Reprod"},{"key":"B13","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.arcmed.2021.01.008","article-title":"Microrna-103 contributes to progression of polycystic ovary syndrome through modulating the Irs1\/Pi3k\/Akt signal axis","volume":"52","author":"Mu","year":"2021","journal-title":"Arch Med Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000605RR","article-title":"Hmgb1-induced aberrant autophagy contributes to insulin resistance in granulosa cells in PCOS","volume":"34","author":"Zhang","year":"2020","journal-title":"FASEB J"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802829R","article-title":"Elevated chemerin induces insulin resistance in human granulosa-lutein cells from polycystic ovary syndrome patients","volume":"33","author":"Li","year":"2019","journal-title":"FASEB J"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-66-1-165","article-title":"Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: Indirect evidence for partial gonadotroph desensitization","volume":"66","author":"Waldstreicher","year":"1988","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154458","article-title":"Direct impact of gonadotropins on glucose uptake and storage in preovulatory granulosa cells: Implications in the pathogenesis of polycystic ovary syndrome","volume":"115","author":"Chahal","year":"2021","journal-title":"Metabolism"},{"key":"B18","article-title":"The impact of Tlr4 on insulin resistance and inflammatory factors in rats with polycystic ovary syndrome","volume":"11","author":"Guo","year":"2018","journal-title":"Int J Clin Exp Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12958-021-00873-3","article-title":"Elevated Saa1 promotes the development of insulin resistance in ovarian granulosa cells in polycystic ovary syndrome","volume":"20","author":"Zhu","year":"2022","journal-title":"Reprod Biol Endocrinol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2018.12.010","article-title":"Comprehensive assessment the expression of core elements related to Igfir\/Pi3k pathway in granulosa cells of women with polycystic ovary syndrome","volume":"233","author":"He","year":"2019","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1177\/1933719117715129","article-title":"Abnormality of Klotho signaling is involved in polycystic ovary syndrome","volume":"25","author":"Mao","year":"2018","journal-title":"Reprod Sci"},{"key":"B22","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s13048-023-01246-7","article-title":"Alteration of the N(6)-methyladenosine methylation landscape in a mouse model of polycystic ovary syndrome","volume":"16","author":"Zou","year":"2023","journal-title":"J Ovarian Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2018.1527307","article-title":"Activating transcriptional factor 4 correlated with obesity and insulin resistance in polycystic ovary syndrome","volume":"35","author":"Di","year":"2019","journal-title":"Gynecol Endocrinol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010134","article-title":"Cysteine-cysteine motif chemokine receptor 5 expression in letrozole-induced polycystic ovary syndrome mice","volume":"23","author":"Seow","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12905-023-02872-5","article-title":"Phlpp1 inhibits the growth and aerobic glycolysis activity of human ovarian granular cells through inactivating Akt pathway","volume":"24","author":"Yang","year":"2024","journal-title":"BMC Womens Health"},{"key":"B26","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1186\/s12905-022-01994-6","article-title":"Up-regulation of Mir-133a-3p promotes ovary insulin resistance on granulosa cells of obese PCOS patients via inhibiting Pi3k\/Akt signaling","volume":"22","author":"Yang","year":"2022","journal-title":"BMC Womens Health"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155164","article-title":"The interactions of Cap and Lyn with the insulin signaling transducer Cbl play an important role in polycystic ovary syndrome","volume":"131","author":"Shen","year":"2022","journal-title":"Metabolism"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167063","article-title":"Grim19 deficiency aggravates metabolic disorder and ovarian dysfunction in PCOS","volume":"1870","author":"Yang","year":"2024","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-022-02676-w","article-title":"Granulosa cells from immature follicles exhibit restricted glycolysis and reduced energy production: A dominant problem in polycystic ovary syndrome","volume":"40","author":"Mazloomi","year":"2023","journal-title":"J Assist Reprod Genet"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.21037\/atm-21-1288","article-title":"Aberrant Mirna-mrna regulatory network in polycystic ovary syndrome is associated with markers of insulin sensitivity and inflammation","volume":"9","author":"Qin","year":"2021","journal-title":"Ann Transl Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.103058","article-title":"Novel Pgk1 determines Skp2-dependent Ar stability and reprograms granular cell glucose metabolism facilitating ovulation dysfunction","volume":"61","author":"Liu","year":"2020","journal-title":"EBioMedicine"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.12.008","article-title":"Long non-coding Rna Lnc-Ccnl1-3:1 promotes granulosa cell apoptosis and suppresses glucose uptake in women with polycystic ovary syndrome","volume":"23","author":"Huang","year":"2021","journal-title":"Mol Ther Nucleic Acids"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1172\/jci12876","article-title":"The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression","volume":"108","author":"Nakae","year":"2001","journal-title":"J Clin Invest"},{"key":"B34","doi-asserted-by":"publisher","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":"Tan","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2033014","article-title":"Microrna-29c-3p participates in insulin function to modulate polycystic ovary syndrome via targeting forkhead box O 3","volume":"13","author":"Chen","year":"2022","journal-title":"Bioengineered"},{"key":"B36","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12958-020-00651-7","article-title":"Expression of angiopoietin-like protein 2 in ovarian tissue of rat polycystic ovarian syndrome model and its correlation study","volume":"18","author":"Wang","year":"2020","journal-title":"Reprod Biol Endocrinol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-020-05730-z","article-title":"Mirnas expression profiling of rat ovaries displaying PCOS with insulin resistance","volume":"302","author":"Zhang","year":"2020","journal-title":"Arch Gynecol Obstet"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-024-10183-8","article-title":"New insights into the treatment of polycystic ovary syndrome: Hkdc1 promotes the growth of ovarian granulocyte cells by regulating mitochondrial function and glycolysis","volume":"55","author":"Cong","year":"2024","journal-title":"J Mol Histol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12964-023-01410-y","article-title":"Bisphenol a downregulates Glut4 expression by activating aryl hydrocarbon receptor to exacerbate polycystic ovary syndrome","volume":"22","author":"Shi","year":"2024","journal-title":"Cell Commun Signal"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-025-04173-0","article-title":"Research mechanism of Dbp and Dehp in the development of PCOS based on network toxicology and molecular docking","volume":"398","author":"Yi-Fan","year":"2025","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23111","article-title":"Nontargeted metabolomic analysis of skeletal muscle in a dehydroepiandrosterone-induced mouse model of polycystic ovary syndrome","volume":"86","author":"Shen","year":"2019","journal-title":"Mol Reprod Dev"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24190","article-title":"Dehydroepiandrosterone-induced activation of Mtorc1 and inhibition of autophagy contribute to skeletal muscle insulin resistance in a mouse model of polycystic ovary syndrome","volume":"9","author":"Song","year":"2018","journal-title":"Oncotarget"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1530\/ec-19-0551","article-title":"Exercise and insulin resistance in PCOS: Muscle insulin signalling and fibrosis","volume":"9","author":"Stepto","year":"2020","journal-title":"Endocr Connect"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11061586","article-title":"Ampk activation as a protective mechanism to restrain oxidative stress in the insulin-resistant state in skeletal muscle of rat model of PCOS subjected to postnatal overfeeding","volume":"11","author":"Mi\u0107i\u0107","year":"2023","journal-title":"Biomedicines"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00195.2017","article-title":"Insulin signaling displayed a differential tissue-specific response to low-dose dihydrotestosterone in female mice","volume":"314","author":"Andrisse","year":"2018","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3892\/or.2018.6375","article-title":"Microrna-33b-5p is overexpressed and inhibits Glut4 by targeting Hmga2 in polycystic ovarian syndrome: An in vivo and in vitro study","volume":"39","author":"Yang","year":"2018","journal-title":"Oncol Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23168942","article-title":"Ampk activation is important for the preservation of insulin sensitivity in visceral, but not in subcutaneous adipose tissue of postnatally overfed rat model of polycystic ovary syndrome","volume":"23","author":"Mi\u0107i\u0107","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B48","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/s13098-023-01155-1","article-title":"Effect of C-reactive protein deficiency on insulin resistance reversal in rats with polycystic ovary syndrome through augmented leptin action","volume":"15","author":"Li","year":"2023","journal-title":"Diabetol Metab Syndr"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/biom15040572","article-title":"Metabolic implications of elevated neutrophil extracellular traps in polycystic ovary syndrome: A focus on hepatic glycolysis","volume":"15","author":"Lin","year":"2025","journal-title":"Biomolecules"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.990987","article-title":"The complex metabolic interactions of liver tissue and hepatic exosome in pcos mice at young and middle age","volume":"13","author":"Gao","year":"2022","journal-title":"Front Physiol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202100961R","article-title":"Androgen-induced insulin resistance is ameliorated by deletion of hepatic androgen receptor in females","volume":"35","author":"Andrisse","year":"2021","journal-title":"FASEB J"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1071\/rd18222","article-title":"Amelioration by quercetin of insulin resistance and uterine glut4 and er\u03b1 gene expression in rats with polycystic ovary syndrome (pcos)","volume":"31","author":"Neisy","year":"2019","journal-title":"Reprod Fertil Dev"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-020-00194-7","article-title":"Hyperandrogenic milieu dysregulates the expression of insulin signaling factors and glucose transporters in the endometrium of patients with polycystic ovary syndrome","volume":"27","author":"Lee","year":"2020","journal-title":"Reprod Sci"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.26402\/jpp.2021.6.13","article-title":"Effect of tnf-alpha on endometrial glucose transporter-4 expression in patients with polycystic ovary syndrome through nuclear factor-kappa b signaling pathway activation","volume":"72","author":"Ha","year":"2021","journal-title":"J Physiol Pharmacol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-02459","article-title":"Local cortisol elevation contributes to endometrial insulin resistance in polycystic ovary syndrome","volume":"103","author":"Qi","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2023.2231085","article-title":"Talin1 regulates glucose metabolism and endometrial receptivity via glut-4 in patients with polycystic ovary syndrome and insulin resistance","volume":"39","author":"Li","year":"2023","journal-title":"Gynecol Endocrinol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14672","article-title":"Autoimmune activation of the gnrh receptor induces insulin resistance independent of obesity in a female rat model","volume":"8","author":"Li","year":"2021","journal-title":"Physiol Rep"},{"key":"B58","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12958-020-00592-1","article-title":"Decreased brain and muscle arnt-like protein 1 expression mediated the contribution of hyperandrogenism to insulin resistance in polycystic ovary syndrome","volume":"18","author":"Zhai","year":"2020","journal-title":"Reprod Biol Endocrinol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.trsl.2020.02.003","article-title":"Altered circadian clock as a novel therapeutic target for constant darkness-induced insulin resistance and hyperandrogenism of polycystic ovary syndrome","volume":"219","author":"Li","year":"2020","journal-title":"Transl Res"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1017147","article-title":"Multi-omics analyses reveal the specific changes in gut metagenome and serum metabolome of patients with polycystic ovary syndrome","volume":"13","author":"Yang","year":"2022","journal-title":"Front Microbiol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqab118","article-title":"Intestinal flora is a key factor in insulin resistance and contributes to the development of polycystic ovary syndrome","volume":"162","author":"Yang","year":"2021","journal-title":"Endocrinology"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1530\/ec-20-0608","article-title":"Androgens impair \u03b2-cell function in a mouse model of polycystic ovary syndrome by activating endoplasmic reticulum stress","volume":"10","author":"Zhu","year":"2021","journal-title":"Endocr Connect"},{"key":"B63","doi-asserted-by":"publisher","first-page":"762","DOI":"10.21037\/atm-22-2941","article-title":"Differential expression of microrna in the serum of patients with polycystic ovary syndrome with insulin resistance","volume":"10","author":"Huo","year":"2022","journal-title":"Ann Transl Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1553","article-title":"Low-dose dihydrotestosterone drives metabolic dysfunction via cytosolic and nuclear hepatic androgen receptor mechanisms","volume":"158","author":"Andrisse","year":"2017","journal-title":"Endocrinology"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0956","article-title":"Reproductive tissues maintain insulin sensitivity in diet-induced obesity","volume":"61","author":"Wu","year":"2012","journal-title":"Diabetes"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1130681","article-title":"Androgen receptor signaling regulates follicular growth and steroidogenesis in interaction with gonadotropins in the ovary during mini-puberty in mice","volume":"14","author":"Devillers","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-022-01091-0","article-title":"Insulin resistance in polycystic ovary syndrome across various tissues: An updated review of pathogenesis, evaluation, and treatment","volume":"16","author":"Zhao","year":"2023","journal-title":"J Ovarian Res"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1097\/RD9.0000000000000131","article-title":"Research progress on insulin resistance in polycystic ovary syndrome","volume":"9","author":"Qi","year":"2025","journal-title":"Reprod Dev Med"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.05.006","article-title":"Molecular mechanisms of insulin resistance in polycystic ovary syndrome","volume":"12","author":"Diamanti-Kandarakis","year":"2006","journal-title":"Trends Mol Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01771","article-title":"Molecular mechanisms in skeletal muscle underlying insulin resistance in women who are lean with polycystic ovary syndrome","volume":"104","author":"Hansen","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00167","article-title":"Molecular mechanisms of insulin resistance in polycystic ovary syndrome: Unraveling the conundrum in skeletal muscle","volume":"104","author":"Stepto","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaf197","article-title":"Insulin resistance in pcos: Pathophysiological mechanisms of menstrual dysfunction and evidence-based treatment strategies","volume":"113","author":"Chen","year":"2025","journal-title":"Biol Reprod"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3390\/medicina60101656","article-title":"The cardiometabolic risk in women with polycystic ovarian syndrome (pcos): From pathophysiology to diagnosis and treatment","volume":"60","author":"Pililis","year":"2024","journal-title":"Med (Kaunas)"},{"key":"B74","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s12967-021-02817-2","article-title":"Eight-hour time-restricted feeding improves endocrine and metabolic profiles in women with anovulatory polycystic ovary syndrome","volume":"19","author":"Li","year":"2021","journal-title":"J Transl Med"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1186\/s12937-020-0524-5","article-title":"The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: A randomized open-labeled controlled clinical trial","volume":"19","author":"Haidari","year":"2020","journal-title":"Nutr J"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0245023","article-title":"Effect of high-intensity interval training on metabolic parameters in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials","volume":"16","author":"Santos","year":"2021","journal-title":"PloS One"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2024.2357737","article-title":"The latest reports and treatment methods on polycystic ovary syndrome","volume":"56","author":"Sta\u0144czak","year":"2024","journal-title":"Ann Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1111\/dom.70452","article-title":"Efficacy of liraglutide on metabolic and reproductive outcomes in women with polycystic ovary syndrome: A systematic review and meta-analysis","volume":"28","author":"Lu","year":"2026","journal-title":"Diabetes Obes Metab"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.25259\/ijmr_497_2025","article-title":"Efficacy & safety of sodium-glucose cotransporter-2 inhibitors in polycystic ovary syndrome: A meta-analysis with trial sequential analysis","volume":"162","author":"Ahsan","year":"2025","journal-title":"Indian J Med Res"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.178055","article-title":"The effects of metformin and sitagliptin for polycystic ovary syndrome treatment are enhanced by combining them","volume":"1005","author":"Kaboutarkhani","year":"2025","journal-title":"Eur J Pharmacol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/cen.14895","article-title":"Oral contraceptives (ocs) in combination with metformin versus ocs alone on metabolism in nonobese polycystic ovary syndrome: A meta-analysis and systematic review of randomized controlled trials","volume":"99","author":"Wu","year":"2023","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c15461","article-title":"Spatiotemporal imaging of mirna in granulosa cells from patients with polycystic ovary syndrome by near-infrared light-activated dna nanoprobes","volume":"20","author":"Cheng","year":"2026","journal-title":"ACS Nano"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2021.100594","article-title":"Melatonin alleviates insulin resistance through the pi3k\/akt signaling pathway in ovary granulosa cells of polycystic ovary syndrome","volume":"22","author":"Guo","year":"2022","journal-title":"Reprod Biol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2019.01.050","article-title":"Serum chemerin levels in polycystic ovary syndrome after metformin therapy","volume":"13","author":"Foda","year":"2019","journal-title":"Diabetes Metab Syndr"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa951","article-title":"Tlr4-associated irf-7 and nf\u03bab signaling act as a molecular link between androgen and metformin activities and cytokine synthesis in the pcos endometrium","volume":"106","author":"Hu","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13186","article-title":"Resveratrol treatment in patients with polycystic ovary syndrome decreased pro-inflammatory and endoplasmic reticulum stress markers","volume":"83","author":"Brenjian","year":"2020","journal-title":"Am J Reprod Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16019","article-title":"Impact of metformin on c-reactive protein levels in women with polycystic ovary syndrome: A meta-analysis","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0756.2012.02051.x","article-title":"Effect of metformin compared with hypocaloric diet on serum c-reactive protein level and insulin resistance in obese and overweight women with polycystic ovary syndrome","volume":"39","author":"Esfahanian","year":"2013","journal-title":"J Obstet Gynaecol Res"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.70506","article-title":"The effects of a novel fortified dairy product on weight loss, metabolic profiles, and endocrine hormones in women with polycystic ovary syndrome: A double-blind randomized controlled trial","volume":"13","author":"Askarpour","year":"2025","journal-title":"Food Sci Nutr"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073922","article-title":"Metformin treatment regulates the expression of molecules involved in adiponectin and insulin signaling pathways in endometria from women with obesity-associated insulin resistance and pcos","volume":"23","author":"Or\u00f3stica","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2013.07.004","article-title":"Inflammatory cytokines and chemokines, skeletal muscle and polycystic ovary syndrome: Effects of pioglitazone and metformin treatment","volume":"62","author":"Ciaraldi","year":"2013","journal-title":"Metabolism"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00162.2019","article-title":"The insulin-sensitizing mechanism of myo-inositol is associated with ampk activation and glut-4 expression in human endometrial cells exposed to a pcos environment","volume":"318","author":"Cabrera-Cruz","year":"2020","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B93","article-title":"Reversing the reduced level of endometrial glut4 expression in polycystic ovary syndrome: A mechanistic study of metformin action","volume":"7","author":"Li","year":"2015","journal-title":"Am J Transl Res"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2014.01.009","article-title":"Metformin modulates pi3k and glut4 expression and akt\/pkb phosphorylation in human endometrial stromal cells after stimulation with androgen and insulin","volume":"175","author":"Ferreira","year":"2014","journal-title":"Eur J Obstet Gynecol Reprod Biol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1810805\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:47:40Z","timestamp":1776055660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1810805\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":94,"alternative-id":["10.3389\/fendo.2026.1810805"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1810805","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]},"article-number":"1810805"}}