2025/09/05 by Zhanat Koshenov, Sandra Postic, Gabriela Schosiwohl +27 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Pancreatic function and diabetes #Metabolism, Diabetes, and Cancer #Calcium signaling and nucleotide metabolism
paper · pdf · doi:10.1101/2025.09.05.674426
openalex publication_date 2025/09/05 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Abstract Presenilin 1 is an endoplasmic reticulum protein, most known for its role in 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.