{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:49:32Z","timestamp":1791874172117,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Perfluorooctanesulfonic acid (PFOS) is epidemiologically linked to gestational diabetes mellitus (GDM), but the mechanisms remain undefined. We hypothesized that PFOS exposure impairs pancreatic \u03b2-cell function through mitochondrial dysfunction and deficits in ATP\/cAMP signaling. Pregnant and non-pregnant rats received PFOS (50\u2009\u03bcg\/mL in drinking water) for 17 days (gestation day [GD] 4\u201320 in pregnant dams). PFOS-exposed pregnant dams exhibited fasting hypoinsulinemia (65% decrease) with normal fasting glucose. Glucose tolerance was impaired (31% increase in glucose AUC), with blunted insulin secretion (52% decrease in insulin AUC). In contrast, non-pregnant PFOS-exposed rats showed no changes in fasting glucose or insulin but developed glucose intolerance (25% increase in glucose AUC) with only modest early insulin suppression, revealing greater vulnerability in pregnancy. Pancreatic islet morphology and insulin content remained unchanged in PFOS-exposed dams. Isolated islets from PFOS-exposed dams and INS-1 \u03b2-cells treated with PFOS (10\u2013100\u2009\u03bcM) showed reduced glucose-stimulated insulin secretion despite normal Ins1 and Ins2 expression and insulin content. In INS-1 cells, PFOS selectively reduced Complex II subunits, depleted ATP (32\u201339%) and cAMP (57\u201374%), and impaired insulin secretion under low and high glucose. Co-treatment with the mitochondria-targeted antioxidant MitoQ (0.1\u03bcM) fully restored ATP, cAMP, and insulin secretion to control levels. These findings demonstrate that PFOS exposure causes gestational glucose intolerance and \u03b2-cell secretory failure, accompanied by reduced mitochondrial Complex II subunit abundance and ATP\/cAMP depletion. The complete rescue by MitoQ highlights oxidative mitochondrial dysfunction as a mechanistic contributor linking PFOS exposure and GDM risk.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag137","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T11:37:06Z","timestamp":1791718626000},"source":"Crossref","is-referenced-by-count":0,"title":["Maternal PFOS Exposure Impairs \u03b2\u2011Cell Insulin Secretion and Glucose Tolerance in Rats"],"prefix":"10.1093","author":[{"given":"Alissa","family":"Hofmann","sequence":"first","affiliation":[{"name":"University of Wisconsin Department of Comparative Biosciences, School of Veterinary Medicine, , Madison, WI 53706,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Yadav","sequence":"additional","affiliation":[{"name":"University of Wisconsin Department of Comparative Biosciences, School of Veterinary Medicine, , Madison, WI 53706,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolin","family":"Song","sequence":"additional","affiliation":[{"name":"University of Wisconsin Department of Comparative Biosciences, School of Veterinary Medicine, , Madison, WI 53706,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sri Vidya","family":"Dangudubiyyam","sequence":"additional","affiliation":[{"name":"University of Wisconsin Department of Comparative Biosciences, School of Veterinary Medicine, , Madison, WI 53706,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay S","family":"Mishra","sequence":"additional","affiliation":[{"name":"University of Wisconsin Department of Comparative Biosciences, School of Veterinary Medicine, , Madison, WI 53706,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathish","family":"Kumar","sequence":"additional","affiliation":[{"name":"University of Wisconsin Department of Comparative Biosciences, School of Veterinary Medicine, , Madison, WI 53706,","place":["USA"]},{"name":"University of Wisconsin Department of Obstetrics and Gynecology, School of Medicine and Public Health, , Madison, WI 53792,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,12]]},"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfag137\/71892554\/kfag137.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfag137\/71892554\/kfag137.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:13:32Z","timestamp":1791872012000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/advance-article\/doi\/10.1093\/toxsci\/kfag137\/8911851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfag137","relation":{},"ISSN":["1096-0929"],"issn-type":[{"value":"1096-0929","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]},"article-number":"kfag137"}}