{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:45:50Z","timestamp":1791852350072,"version":"4.3.4"},"reference-count":22,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"JSPS KAKENHI","award":["Grant Nos. 19K07498, 24K11670 to S.O."],"award-info":[{"award-number":["Grant Nos. 19K07498, 24K11670 to S.O."]}]},{"name":"This work was partly supported by the Joint Research Program of the Joint Usage\/Research Center at IDAC, Tohoku University","award":["Grant Nos. 8 [2019], 10 [2020], 38 [2021], 29 [2022], 20 [2023], 27 [2024], and 27 [2025]"],"award-info":[{"award-number":["Grant Nos. 8 [2019], 10 [2020], 38 [2021], 29 [2022], 20 [2023], 27 [2024], and 27 [2025]"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Transgenic mice expressing the C414A-mutant cryptochrome 1 (CRY1 C414A) develop diabetes with progressive \u03b2-cell senescence and the formation of mucinous intra-islet ductal lesions. These lesions exhibit features resembling metaplasia; however, their molecular basis and the potential involvement of endocrine cells remain unclear. This study aimed to define the metaplasia-like program in intra-islet ducts and to characterize endocrine cell phenotypes in this context.<\/jats:p>\n                  <jats:p>Gene expression microarrays were analyzed using islets from aged CRY1 C414A transgenic and wild-type mice. Histological analyses included Alcian blue staining, lectin labeling, and immunostaining for markers of mucin production, metaplasia, and endocrine differentiation. Marker expression in intra-islet ductal lesions was evaluated to assess their progression and cellular composition.<\/jats:p>\n                  <jats:p>Transgenic islets exhibited upregulated expression of metaplasia-associated genes, including mucin 6, trefoil factor 2, and gastrokine 3. Intra-islet ducts, particularly smaller lesions, showed strong mucin production and co-expression of metaplasia-related markers. Tuft cell\u2013associated markers were detected in both intra-islet lesions and pancreatic duct glands. In addition, subsets of insulin-positive cells adjacent to lesions exhibited reduced insulin granularity and expression of metaplasia markers, while glucagon-positive cells were prominent in early lesions.<\/jats:p>\n                  <jats:p>Intra-islet ductal lesion formation in CRY1 C414A transgenic mice is associated with activation of a pyloric\/spasmolytic polypeptide\u2013expressing metaplasia-like metaplastic program and endocrine cell plasticity. These findings provide a framework linking intra-islet duct formation to established metaplastic processes and suggest a potential relationship \u03b2-cell dedifferentiation and broader endocrine cell plasticity under chronic islet stress.<\/jats:p>","DOI":"10.1055\/a-2968-0251","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:14:56Z","timestamp":1790378096000},"source":"Crossref","is-referenced-by-count":0,"title":["Intra-Islet Duct Formation and Gastric-Type Metaplasia in CRY1 C414A Transgenic Mice: Associations with Endocrine Cell Plasticity and \u03b1-Cell Localization"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1272-4981","authenticated-orcid":false,"given":"Satoshi","family":"Okano","sequence":"additional","affiliation":[{"name":"Yamagata University, Japan","place":["Yamagata"],"department":["Graduate School of Medical Science, Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Yamagata University, Japan","place":["Yamagata"],"department":["Department of Gastroenterology, Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yasui","sequence":"additional","affiliation":[{"name":"Tohoku University, Japan","place":["Sendai"],"department":["Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging and Cancer"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennichi","family":"Satoh","sequence":"additional","affiliation":[{"name":"Tohoku Medical and Pharmaceutical University, Japan","place":["Sendai"],"department":["Division of Gastroenterology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Takahata Public Hospital, Japan","place":["Yamagata"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Yamagata University, Japan","place":["Yamagata"],"department":["Graduate School of Medical Science, Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.neulet.2009.01.014","article-title":"Unusual circadian locomotor activity and pathophysiology in mutant CRY1 transgenic mice","volume":"451","author":"S Okano","year":"2009","journal-title":"Neurosci Lett"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s41105-016-0050-1","article-title":"Unique food-entrained circadian rhythm in cysteine414-alanine mutant mCRY1 transgenic mice","volume":"14","author":"S 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