{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:06:41Z","timestamp":1790089601979,"version":"4.0.1"},"reference-count":0,"publisher":"American Diabetes Association","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"Novo-Nordisk Scholarships"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CRC-2024-00146"],"award-info":[{"award-number":["CRC-2024-00146"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-69018"],"award-info":[{"award-number":["MOP-69018"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-166061"],"award-info":[{"award-number":["PJT-166061"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-180576"],"award-info":[{"award-number":["PJT-180576"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-195911"],"award-info":[{"award-number":["PJT-195911"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ontario Graduate Scholarships"},{"name":"Banting and Best Diabetes Centre"},{"DOI":"10.13039\/100013528","name":"Diabetes Canada","doi-asserted-by":"publisher","award":["OG-3-21-56"],"award-info":[{"award-number":["OG-3-21-56"]}],"id":[{"id":"10.13039\/100013528","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Showa University Research Grant for Young Researchers","id":[{"id":"https:\/\/ror.org\/04mzk4q39","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>The intracellular nucleotide-binding oligomerization domain (Nod) receptors of innate immunity have been demonstrated to play a significant role in metabolism. Saturated fatty acids have been reported to directly activate Nods, and deletion of Nod1 protects against glucose intolerance induced by a high-fat diet. This suggests a role for Nod1 in \u03b2-cells because glucose tolerance is heavily determined by \u03b2-cell performance. Therefore, we hypothesized that saturated fatty acid\u2013induced \u03b2-cell dysfunction is mediated in part by Nod1 in the \u03b2-cell. Both mouse and human islets express Nod1 mRNA. Treatment with the Nod1 ligands C12 iE-DAP and FK565 decreased \u03b2-cell function in\u00a0vitro and in\u00a0vivo, respectively, in male mice. Mechanistically, this was mediated by JNK and IKK\u03b2 activation, because islets from JNK1-knockout (KO) and \u03b2-cell\u2013specific IKK\u03b2-KO mice were protected against Nod1 ligand\u2013induced dysfunction. In vitro, islets of Nod1-KO mice were protected from palmitate-induced \u03b2-cell dysfunction. Similarly, in\u00a0vivo, whole-body or \u03b2-cell\u2013specific Nod1-KO mice were protected from palmitate-induced \u03b2-cell dysfunction during hyperglycemic clamps. Together, these data demonstrate that Nod1 plays a causal role in saturated fatty acid\u2013induced \u03b2-cell dysfunction in\u00a0vitro and in\u00a0vivo in male mice.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>The innate immunity receptor nucleotide-binding oligomerization domain 1 (Nod1) can be activated by saturated fatty acids and is implicated in high-fat diet-induced inflammation and insulin resistance. This implies Nod1 plays a role in glucose homeostasis; therefore, we sought to determine whether saturated fatty acids cause pancreatic \u03b2-cell dysfunction through Nod1. Our data demonstrate that Nod1 is involved in palmitate-induced \u03b2-cell dysfunction in\u00a0vitro and in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0752","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:44:41Z","timestamp":1790088281000},"update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Nod1 Plays a Causal Role in Palmitate-Induced \u03b2-Cell Dysfunction In\u00a0Vitro and In\u00a0Vivo in Male Mice"],"prefix":"10.2337","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5906-7558","authenticated-orcid":false,"given":"Justin H.M.","family":"Yung","sequence":"first","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"2Duke-NUS Medical School, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily G.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"3Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Ivovic","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.M. Niazur","family":"Rahman","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"4College of Dentistry, Al Ain University, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tejas","family":"Desai","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khajag","family":"Koulajian","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusaku","family":"Mori","sequence":"additional","affiliation":[{"name":"5Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine, Shinagawa, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Maisonneuve","sequence":"additional","affiliation":[{"name":"6Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marry","family":"Nissan","sequence":"additional","affiliation":[{"name":"6Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Bengisu","family":"Gelmez","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"3Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Rabiee","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"3Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Pereira","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"7Centre for Addiction and Mental Health, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Al-Rijjal","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"3Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana J.","family":"Philpott","sequence":"additional","affiliation":[{"name":"6Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2246-5821","authenticated-orcid":false,"given":"Adria","family":"Giacca","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"3Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada"},{"name":"8Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"9Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9653-2828","authenticated-orcid":false,"given":"Kacey J.","family":"Prentice","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"3Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,9,22]]},"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db25-0752\/896172\/db250752.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/doi\/10.2337\/db25-0752\/896172\/db250752.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:44:42Z","timestamp":1790088282000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/doi\/10.2337\/db25-0752\/172556\/Nod1-Plays-a-Causal-Role-in-Palmitate-Induced-Cell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":0,"URL":"https:\/\/doi.org\/10.2337\/db25-0752","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"db250752"}}