{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T06:34:32Z","timestamp":1787380472504,"version":"build-2736575974"},"reference-count":82,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK123163"],"award-info":[{"award-number":["R01DK123163"]}],"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":["R01DK133838"],"award-info":[{"award-number":["R01DK133838"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007878","name":"Diabetes Research Center","doi-asserted-by":"publisher","award":["P30 DK020579"],"award-info":[{"award-number":["P30 DK020579"]}],"id":[{"id":"10.13039\/100007878","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007878","name":"Diabetes Research Center","doi-asserted-by":"publisher","award":["P30 DK056341"],"award-info":[{"award-number":["P30 DK056341"]}],"id":[{"id":"10.13039\/100007878","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sulfonylureas, commonly used to treat type 2 diabetes (T2D), often lose effectiveness over time when used as monotherapy; however, the underlying mechanisms remain unclear. To investigate the mechanisms of sulfonylurea failure, glibenclamide\u2010releasing pellets were implanted in KK mice, a polygenic model that spontaneously develops T2D. KK mice receiving placebo pellets (KK\u2010Placebo) developed hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance. Notably, KK mice implanted with glibenclamide (KK\u2010Glib) showed improved blood glucose levels during the first 7 days, returning to KK\u2010Placebo levels thereafter. KK\u2010Glib mice exhibited reduced plasma insulin levels and insulin secretion in response to a glucose challenge compared with the markedly elevated levels in KK\u2010Placebo mice. KK\u2010Glib mice showed islet hypertrophy, reduced \u03b2\u2010cell mass and number, and increased \u03b1\u2010cell number, resulting in elevated \u03b1:\u03b2 cell ratio compared with KK\u2010Placebo. Although mRNA expression of \u03b2\u2010cell identity markers remained unchanged, their protein levels were reduced in KK\u2010Glib, suggesting \u03b2\u2010cell identity loss, which may underlie the observed impaired insulin secretion. Remarkably, KK\u2010Glib mice showed elevated mRNA levels of\n                    <jats:italic>Ngn3<\/jats:italic>\n                    (dedifferentiation) and \u03b1\u2010cell identity markers along with glucagon content, suggesting \u03b1\u2010cell neogenesis. These findings suggest that secondary failure of sulfonylurea therapy may, in part, result from loss of \u03b2\u2010cell identity\u2010function and increased \u03b1\u2010cell number\u2010identity.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70588","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T07:35:59Z","timestamp":1770708959000},"source":"Crossref","is-referenced-by-count":2,"title":["Loss of Beta\u2010Cell Identity and Function as a Mechanism of Secondary Failure of Sulfonylurea Therapy in Diabetes"],"prefix":"10.1002","volume":"7","author":[{"given":"Sumit","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Endocrinology Metabolism and Lipid Research School of Medicine Washington University in St Louis  St Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Endocrinology Metabolism and Lipid Research School of Medicine Washington University in St Louis  St Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria S.","family":"Remedi","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Endocrinology Metabolism and Lipid Research School of Medicine Washington University in St Louis  St Louis Missouri USA"},{"name":"Deparment of Cell Biology and Physiology School of Medicine Washington University in St Louis  St Louis Missouri USA"},{"name":"Center For the Investigation of Membrane Excitability Diseases School of Medicine Washington University in St Louis  St Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"IDF Diabetes Atlas","author":"Federation ID"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/nyas.12031","article-title":"Islet Beta Cell Mass in Diabetes and How It Relates to Function, Birth, and Death","volume":"1281","author":"Weir G. 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