{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:59:35Z","timestamp":1790341175389,"version":"4.1.0"},"reference-count":117,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Insulin signaling in polycystic ovary syndrome (PCOS) or Polyendocrine Metabolic Ovarian Syndrome (PMOS) involves selective pathway alterations that link metabolic disease to reproductive pathology. In metabolic pathways, impaired PI3K\/Akt signaling limits insulin-dependent GLUT4-mediated glucose intake, while ovarian steroidogenic responses to insulin are preserved. Compensatory pancreatic \u03b2-cell insulin secretion and reduced hepatic insulin clearance lead to hyperinsulinemia, suppressing sex hormone-binding globulin, increasing free androgen bioavailability, and amplifying ovarian androgen production. In ovarian theca cells, hyperinsulinemia results in excess androgen secretion, while granulosa cells demonstrate reduced glucose uptake, estradiol production, and follicular maturation largely due to metabolic insulin resistance. Collectively, these alterations across hepatic, skeletal muscle, adipose, and lipid-metabolic tissues reinforce an insulin-dependent hyperandrogenemia further amplified by obesity and hyperleptinemia. Resultantly, women with PCOS\/PMOS frequently present with both reproductive dysfunction and metabolic syndrome. Therefore, treatment approaches are tailored to individual patient circumstances and generally include lifestyle modification to assist with weight management and improve insulin sensitivity, which may be bolstered by the use of insulin sensitizers like metformin and incretin analogs (GLP1As) that promote weight loss, attenuate insulin resistance, and suppress hepatic gluconeogenesis. Other insulin-sensitizing agents hold promise as evidence evolves. In this review, we summarize how altered insulin signaling plays a prominent role in PCOS\/PMOS pathophysiology and discuss the current evidence for lifestyle and pharmacologic strategies to improve the metabolic and reproductive dysfunction in this syndrome.<\/jats:p>","DOI":"10.3389\/fendo.2026.1955884","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:00:38Z","timestamp":1790337638000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Insulin signaling in PCOS\/PMOS: molecular insights and clinical implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Abhishek","family":"Goel","sequence":"first","affiliation":[{"name":"Clinical Research Branch (CRB), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH)","place":["Research Triangle Park, NC, United 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