article published yes Zhanat Koshenov author Sandra Postic author Gabriela Schoiswohl author Savina Van Amsterdam author Victoria Hois-Zelinka author Furkan E. Oflaz author Rene Rost author Oleksandra Tiapko author Benjamin Gottschalk author Martin Hirtl author Olaf G. Bachkoenig author Aigerim Koshenova author Yusuf C. Erdogan author Adlet Sagintayev author Anita Krnjic author Johannes U. Pfabe author Srdjan Sarikas author 35F0286E-F248-11E8-B48F-1D18A9856A87 Bernhard Hochreiter author e6cab3de-17f6-11ed-9210-c1e42e045e9d Juergen Gindlhuber author Matthias Schittmayer author Jelena Tadic author Barbara Ehall author Frank Madeo author Tobias Madl author Roland Malli author Ruth Birner-Gruenberger author Thomas Pieber author Tobias Eisenberg author Marjan Slak Rupnik author Wolfgang F. Graier author FISS department Presenilin-1 (PS1) is an endoplasmic reticulum protein, most known for its role in pathogenesis of familial Alzheimer’s Disease (AD). PS1 has been attributed roles in intracellular calcium homeostasis in the brain, as well as in the pancreatic beta cells, where it has been shown to be fundamental for the initial phase of glucose-induced insulin secretion. To gain mechanistic insight into beta cell autonomous function of PS1, we have examined various beta cell models and found that PS1 controls glycolytic flux of pancreatic beta cells by regulating sub-mitochondrial Ca2+ homeostasis. Transient knock down of PS1 yielded a glycolytic bottleneck at the step catalyzed by glyceraldehyde-3-phosphate dehydrogenase, resulting in defective glucose responsiveness. Moreover, we show that PS1 is needed for the preservation of beta cell identity, likely due to its role in glycolysis. Finally, we show that mouse islets from an in vivo model of AD mimic the defective glucose responsiveness seen in beta cells with transient PS1 knock down, while the identity loss and whole-body glucose homeostasis are not severely impacted, suggesting an adaptive response. Thus, the current work highlights beta cell autonomous role of PS1 and adds a layer of complexity in its impact on whole body metabolism. https://research-explorer.ista.ac.at/download/23148/23161/2026_CommunicationsBiology_Koshenov.pdf application/pdfno Springer Nature2026 eng 2399-3642 4238703910.1038/s42003-026-10581-6 9 Z. Koshenov <i>et al.</i>, “Presenilin-1 controls glycolysis and identity of pancreatic beta cells,” <i>Communications Biology</i>, vol. 9. Springer Nature, 2026. Koshenov Z, Postic S, Schoiswohl G, Van Amsterdam S, Hois-Zelinka V, Oflaz FE, Rost R, Tiapko O, Gottschalk B, Hirtl M, Bachkoenig OG, Koshenova A, Erdogan YC, Sagintayev A, Krnjic A, Pfabe JU, Sarikas S, Hochreiter B, Gindlhuber J, Schittmayer M, Tadic J, Ehall B, Madeo F, Madl T, Malli R, Birner-Gruenberger R, Pieber T, Eisenberg T, Slak Rupnik M, Graier WF. 2026. Presenilin-1 controls glycolysis and identity of pancreatic beta cells. Communications Biology. 9, 1315. Z. Koshenov, S. Postic, G. Schoiswohl, S. Van Amsterdam, V. Hois-Zelinka, F.E. Oflaz, R. Rost, O. Tiapko, B. Gottschalk, M. Hirtl, O.G. Bachkoenig, A. Koshenova, Y.C. Erdogan, A. Sagintayev, A. Krnjic, J.U. Pfabe, S. Sarikas, B. Hochreiter, J. Gindlhuber, M. Schittmayer, J. Tadic, B. Ehall, F. Madeo, T. Madl, R. Malli, R. Birner-Gruenberger, T. Pieber, T. Eisenberg, M. Slak Rupnik, W.F. Graier, Communications Biology 9 (2026). Koshenov, Zhanat, Sandra Postic, Gabriela Schoiswohl, Savina Van Amsterdam, Victoria Hois-Zelinka, Furkan E. Oflaz, Rene Rost, et al. “Presenilin-1 Controls Glycolysis and Identity of Pancreatic Beta Cells.” <i>Communications Biology</i>. Springer Nature, 2026. <a href="https://doi.org/10.1038/s42003-026-10581-6">https://doi.org/10.1038/s42003-026-10581-6</a>. Koshenov Z, Postic S, Schoiswohl G, et al. Presenilin-1 controls glycolysis and identity of pancreatic beta cells. <i>Communications Biology</i>. 2026;9. doi:<a href="https://doi.org/10.1038/s42003-026-10581-6">10.1038/s42003-026-10581-6</a> Koshenov, Zhanat, et al. “Presenilin-1 Controls Glycolysis and Identity of Pancreatic Beta Cells.” <i>Communications Biology</i>, vol. 9, 1315, Springer Nature, 2026, doi:<a href="https://doi.org/10.1038/s42003-026-10581-6">10.1038/s42003-026-10581-6</a>. Koshenov, Z., Postic, S., Schoiswohl, G., Van Amsterdam, S., Hois-Zelinka, V., Oflaz, F. E., … Graier, W. F. (2026). Presenilin-1 controls glycolysis and identity of pancreatic beta cells. <i>Communications Biology</i>. Springer Nature. <a href="https://doi.org/10.1038/s42003-026-10581-6">https://doi.org/10.1038/s42003-026-10581-6</a> 231482026-10-18T22:01:50Z2026-10-19T06:23:26Z