Hahn, Maxvan Krieken, Pim P.Nord, ChristofferAlanentalo, TomasMorini, FedericoXiong, YanEriksson, MariaMayer, Jürgen, 1977-Kostromina, ElenaRuas, Jorge L.Sharpe, JamesPereira, TeresaBerggren, Per-OlofIlegems, ErwinAhlgren, Ulf2020-11-102020-11-102020Hahn M, van Krieken PP, Nord C, Alanentalo T, Morini F, Xiong Y, Eriksson M, Mayer J, Kostromina E, Ruas JL, Sharpe J, Pereira T, Berggren PO, Ilegems E, Ahlgren U. Topologically selective islet vulnerability and self-sustained downregulation of markers for β-cell maturity in streptozotocin-induced diabetes. Commun Biol. 2020; 3(1):541. DOI: 10.1038/s42003-020-01243-22399-3642http://hdl.handle.net/10230/45694Mouse models of Streptozotocin (STZ) induced diabetes represent the most widely used preclinical diabetes research systems. 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 β-cell mass (BCM) dynamics and islet longevity in STZ-treated mice. We demonstrate that STZ-induced β-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 β-cells but display pancreas-wide downregulation of glucose transporter type 2 (GLUT2). Islet gene expression studies confirmed this downregulation and revealed impaired β-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 β-cell dysfunction rather than β-cell ablation and that hyperglycemia in itself sustains a negative feedback loop restraining islet function recovery.application/pdfeng© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s42003-020-01243-23-D reconstructionDiabetesExperimental models of diseaseMechanisms of diseaseOptical imaginginfo:eu-repo/semantics/openAccess