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September 5th, 2025
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Medical University of Graz
cell biology
bioRxiv

Presenilin-1 controls glucose metabolism and identity of pancreatic beta cells

Koshenov, Z.Open in Google Scholar•Postic, S.Open in Google Scholar•Schosiwohl, G.Open in Google Scholar•van Amsterdam, S.Open in Google Scholar•Hois-Zelinka, V.Open in Google Scholar•Oflaz, F. E.Open in Google Scholar•Rost, R.Open in Google Scholar•Tiapko, O.Open in Google Scholar•Gottschalk, B.Open in Google Scholar•Hirtl, M.Open in Google Scholaret al.

Presenilin 1 is an endoplasmic reticulum protein, most known for its role in the pathogenesis of familial Alzheimer\'s Disease (AD). Presenilin 1 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 glucose-induced insulin secretion. Functional similarity of presenilin 1 in regulation of intracellular calcium homeostasis in the brain and pancreas prompted us to investigate a prevalent assumption that associates AD and diabetes mellitus. By examining pancreatic islets from AD model mice, we have found deficits in initial phase of glucose-induced calcium signaling and insulin secretion. Furthermore, these transgenic mice showed a tendency towards reduced expression of mature beta cell markers, which was even more pronounced in islets and beta cell lines with a transient knock down of presenilin 1. We demonstrate here that presenilin 1 controls beta cell glycolysis by regulating sub-cellular calcium homeostasis and, in doing so, contributes to preservation of beta cell identity

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