Instytut Biotechnologii / Institute of Biotechnology

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Glucotoxicity is mediated by cytoplasmic distribution of RAP1 in pancreatic β-cells
(Elsevier, 2024-03-28) Deręgowska, Anna; Tomaszek, Natalia; Cuch, Patrycja; Kozioł, Katarzyna; Kaniuka, Olga; Sabadashka, Mariya; Bandura, Yurii; Sybirna, Nataliia
Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by persistent hyperglycemia. In our study, we analyzed the level and location of RAP1 changes in the development of β-cell dysfunction induced by glucotoxicity. We employed three pancreatic β-cell lines, namely INS-1, 1.2B4, and NIT-1, as well as a streptozotocin-induced diabetes rat model. We demonstrate that after high glucose treatment, RAP1 is increased, probably through induction by AKT, allowing RAP1 to shuttle from the nucleus to the cytoplasm and activate NF-κB signaling. Furthermore, non-enzymatic post-translational modifications of RAP1, such as advanced glycation end products and carbonylation may affect the function of RAP1, such as activation of the NF-κB signaling. Taken together, we showed that RAP1 is a new player in the mechanism of glucotoxicity in pancreatic β-cells.