{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:57:53Z","timestamp":1791568673253,"version":"4.3.4"},"reference-count":24,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK-098506"],"award-info":[{"award-number":["DK-098506"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK-017047"],"award-info":[{"award-number":["P30 DK-017047"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dick and Julia McAbee Endowed Postdoctoral Fellowship from the University of Washington"},{"DOI":"10.13039\/501100008966","name":"Soci\u00e9t\u00e9 Francophone du Diab\u00e8te","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008966","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001491","name":"Belgian American Educational Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010563","name":"Fonds Baillet Latour","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010563","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Association Belge du Diab\u00e8te"},{"name":"Fondation Horlait-Dapsens"},{"DOI":"10.13039\/501100006673","name":"Fondation L\u00e9on Fredericq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006673","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neprilysin is a ubiquitous peptidase that can modulate glucose homeostasis by cleaving insulinotropic peptides. While global deletion of neprilysin protects mice against high-fat diet (HFD)-induced insulin secretory dysfunction, strategies to ablate neprilysin in a tissue-specific manner are favored to limit off-target effects. Since insulinotropic peptides are produced in the gut, we sought to determine whether gut-specific neprilysin deletion confers beneficial effects on insulin secretion similar to that of global neprilysin deletion in mice fed a HFD. Mice with conditional deletion of neprilysin in enterocytes (NEPGut\u2212\/\u2212) were generated by crossing Vil-Cre and floxed neprilysin mice. Neprilysin activity was almost abolished throughout the gut in NEPGut\u2212\/\u2212 mice, and was similar in plasma, pancreas, and kidney in NEPGut\u2212\/\u2212 vs control mice. An oral glucose tolerance test was performed at baseline and following 14 weeks of HFD feeding, during which glucose tolerance and glucose-stimulated insulin secretion (GSIS) were assessed. Despite similar body weight gain at 14 weeks, NEPGut\u2212\/\u2212 displayed lower fasting plasma glucose levels, improved glucose tolerance, and increased GSIS compared to control mice. In conclusion, gut-specific neprilysin deletion recapitulates the enhanced GSIS seen with global neprilysin deletion in HFD-fed mice. Thus, strategies to inhibit neprilysin specifically in the gut may protect against fat-induced glucose intolerance and beta-cell dysfunction.<\/jats:p>","DOI":"10.1210\/endocr\/bqae080","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T13:14:49Z","timestamp":1719926089000},"source":"Crossref","is-referenced-by-count":3,"title":["Gut-specific Neprilysin Deletion Protects Against Fat-induced Insulin Secretory Dysfunction in Male Mice"],"prefix":"10.1210","volume":"165","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1823-3817","authenticated-orcid":false,"given":"Nathalie","family":"Esser","sequence":"first","affiliation":[{"name":"Research Service, Veterans Affairs Puget Sound Health Care System , Seattle, WA 98108 ,","place":["USA"]},{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington , Seattle, WA 98195 ,","place":["USA"]},{"name":"Laboratory of Immunometabolism and Nutrition, GIGA-R, CHU Li\u00e8ge, University of Li\u00e8ge , Li\u00e8ge 4000 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M","family":"Mongovin","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Puget Sound Health Care System , Seattle, WA 98108 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-7474","authenticated-orcid":false,"given":"Breanne M","family":"Barrow","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Puget Sound Health Care System , Seattle, WA 98108 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4831-7034","authenticated-orcid":false,"given":"Sakeneh","family":"Zraika","sequence":"additional","affiliation":[{"name":"Research Service, Veterans Affairs Puget Sound Health Care System , Seattle, WA 98108 ,","place":["USA"]},{"name":"Division of 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