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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 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s42003-026-10581-6","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:59:32Z","timestamp":1782878372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Presenilin-1 controls glycolysis and identity of pancreatic beta 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