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We applied state of the art optical imaging schemes, spanning from single islet resolution to the whole organ, providing a first longitudinal, 3D-spatial and quantitative account of \u03b2-cell mass (BCM) dynamics and islet longevity in STZ-treated mice. We demonstrate that STZ-induced \u03b2-cell destruction predominantly affects large islets in the pancreatic core. Further, we show that hyperglycemic STZ-treated mice still harbor a large pool of remaining \u03b2-cells but display pancreas-wide downregulation of glucose transporter type 2 (GLUT2). Islet gene expression studies confirmed this downregulation and revealed impaired \u03b2-cell maturity. Reversing hyperglycemia by islet transplantation partially restored the expression of markers for islet function, but not BCM. Jointly our results indicate that STZ-induced hyperglycemia results from \u03b2-cell dysfunction rather than \u03b2-cell ablation and that hyperglycemia in itself sustains a negative feedback loop restraining islet function recovery.<\/jats:p>","DOI":"10.1038\/s42003-020-01243-2","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T10:03:01Z","timestamp":1601460181000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Topologically selective islet vulnerability and self-sustained downregulation of markers for \u03b2-cell maturity in streptozotocin-induced diabetes"],"prefix":"10.1038","volume":"3","author":[{"given":"Max","family":"Hahn","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0501-3076","authenticated-orcid":false,"given":"Pim P.","family":"van Krieken","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-6844","authenticated-orcid":false,"given":"Christoffer","family":"Nord","sequence":"additional","affiliation":[]},{"given":"Tomas","family":"Alanentalo","sequence":"additional","affiliation":[]},{"given":"Federico","family":"Morini","sequence":"additional","affiliation":[]},{"given":"Yan","family":"Xiong","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Eriksson","sequence":"additional","affiliation":[]},{"given":"J\u00fcrgen","family":"Mayer","sequence":"additional","affiliation":[]},{"given":"Elena","family":"Kostromina","sequence":"additional","affiliation":[]},{"given":"Jorge L.","family":"Ruas","sequence":"additional","affiliation":[]},{"given":"James","family":"Sharpe","sequence":"additional","affiliation":[]},{"given":"Teresa","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"Per-Olof","family":"Berggren","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5873-1186","authenticated-orcid":false,"given":"Erwin","family":"Ilegems","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5923-8572","authenticated-orcid":false,"given":"Ulf","family":"Ahlgren","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"1243_CR1","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/S2213-8587(18)30051-2","volume":"6","author":"E Ahlqvist","year":"2018","unstructured":"Ahlqvist, E. et al. 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