{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:13:56Z","timestamp":1783566836715,"version":"3.55.0"},"reference-count":63,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM121334"],"award-info":[{"award-number":["P20GM121334"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM104357"],"award-info":[{"award-number":["P20GM104357"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R21DK113500"],"award-info":[{"award-number":["R21DK113500"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01HL51971"],"award-info":[{"award-number":["P01HL51971"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have a high prevalence of obesity, insulin resistance (IR), increased blood pressure (BP), and activation of the renin angiotensin system (RAS). Effective evidence-based therapeutics to ameliorate the cardiometabolic complications in PCOS are lacking. The sodium-glucose cotransporter-2 (SGLT2) inhibitor Empagliflozin (EMPA) reduces BP and hyperglycemia in type 2 diabetes mellitus. We hypothesized that hyperandrogenemia upregulates renal SGLT2 expression and that EMPA ameliorates cardiometabolic complications in a hyperandrogenemic PCOS model. Four-week-old female Sprague Dawley rats were treated with dihydrotestosterone (DHT) for 90 days, and EMPA was co-administered for the last three weeks. DHT upregulated renal SGLT2, SGLT4, and GLUT2, but downregulated SGLT3 mRNA expression. EMPA decreased DHT-mediated increases in fat mass, plasma leptin, and BP, but failed to decrease plasma insulin, HbA1c, or albuminuria. EMPA decreased DHT-mediated increase in renal angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), and angiotensin II type 1 receptor (AGT1R) mRNA and protein expression. In summary, SGLT2 inhibition proved beneficial in adiposity and BP reduction in a hyperandrogenemic PCOS model; however, additional therapies may be needed to improve IR and renal injury.<\/jats:p>","DOI":"10.3390\/ijms22052576","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T21:58:07Z","timestamp":1614895087000},"page":"2576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5440-9413","authenticated-orcid":false,"given":"Jacob E.","family":"Pruett","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar D.","family":"Torres Fernandez","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3452-4369","authenticated-orcid":false,"given":"Steven J.","family":"Everman","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth M.","family":"Vinson","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8660-0135","authenticated-orcid":false,"given":"Kacey","family":"Davenport","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelyn K.","family":"Logan","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7268-9690","authenticated-orcid":false,"given":"Damian G.","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Women\u2019s Health Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Cardio Renal Research Center, University of Mississippi Medical Center, Jackson, MS  39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7295-1871","authenticated-orcid":false,"given":"Licy L.","family":"Yanes Cardozo","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Women\u2019s Health Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Cardio Renal Research Center, University of Mississippi Medical Center, Jackson, MS  39216, USA"},{"name":"Division of Endocrinology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1093\/humrep\/dew218","article-title":"The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis","volume":"31","author":"Bozdag","year":"2016","journal-title":"Hum. 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