{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:28:07Z","timestamp":1783384087072,"version":"3.54.6"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T00:00:00Z","timestamp":1604707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Type 2 diabetes (T2D) is driven by progressive dysfunction and loss of pancreatic \u03b2\u2010cell mass. Imeglimin is a first\u2010in\u2010class novel drug candidate that improves glycaemia and glucose\u2010stimulated insulin secretion in preclinical models and patients. Given evidence that imeglimin can attenuate \u03b2\u2010cell dysfunction and protect \u03b2 cells <jats:italic>in vitro<\/jats:italic>, we postulated that imeglimin could also exert longer term effects to prevent pancreatic \u03b2\u2010cell death and preserve functional \u03b2\u2010cell mass <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Zucker diabetic fatty (ZDF) male rats were treated by oral gavage with imeglimin at a standard dose of 150 mg\/kg or vehicle, twice daily for five weeks. At treatment completion, oral glucose tolerance tests were performed in fasted animals before a thorough histomorphometry and immunohistochemical analysis was conducted on pancreas tissue slices to assess cellular composition and disease status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Imeglimin treatment significantly improved glucose\u2010stimulated insulin secretion (augmentation of the insulinogenic index) and improved glycaemia. Both basal insulinaemia and pancreatic insulin content were also increased by imeglimin. In ZDF control rats, islet structure was disordered with few \u03b2\u2010cells; after imeglimin treatment, islets appeared healthier with more normal morphology in association with a significant increase in insulin\u2010positive \u03b2\u2010cells. The increase in \u03b2\u2010cell mass was associated with a greater degree of \u03b2\u2010cell proliferation in the presence of reduced apoptosis. Unexpectedly, a decrease in as a \u03b1\u2010cell mass was also documented due to an apparent antiproliferative effect of imeglimin on this cell type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In male ZDF rats, chronic imeglimin treatment corrects a paramount component of type 2 diabetes progression: progressive loss of functional \u03b2\u2010cell mass. In addition, imeglimin may also moderate a\u2010cell turnover to further ameliorate hyperglycaemia. Cumulatively, these cellular effects suggest that imeglimin may provide for disease modifying effects to preserve functional \u03b2\u2010cell mass.<\/jats:p><\/jats:sec>","DOI":"10.1002\/edm2.193","type":"journal-article","created":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T08:55:41Z","timestamp":1604739341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Imeglimin preserves islet \u03b2\u2010cell mass in Type 2 diabetic ZDF rats"],"prefix":"10.1002","volume":"4","author":[{"given":"Sophie","family":"Hallakou\u2010Bozec","sequence":"first","affiliation":[{"name":"Poxel SA Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micheline","family":"Kergoat","sequence":"additional","affiliation":[{"name":"Metabrain Research Maisons\u2010Alfort 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