Kolegium Nauk Przyrodniczych / College of Natural Sciences

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Browsing Kolegium Nauk Przyrodniczych / College of Natural Sciences by Author "Bandura, Yurii"

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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.
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    Upregulation of GRP78 is accompanied by decreased antioxidant response and mitophagy promotion in streptozotocin-induced type 1 diabetes in rats - original data
    (Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2024-09-25) Kaniuka, Olena; Deręgowska, Anna; Bandura, Yurii; Sabadashka, Mariya; Chala, Dariya; Kulachkovskyi, Olexandr; Kubis, Hubert; Adamczyk-Grochala, Jagoda; Sybirna, Nataliia
    Endoplasmic reticulum stress, oxidative stress, and mitochondrial dysfunction are interconnected processes involved in the pathogenesis of diabetes mellitus (DM). In the present study, we demonstrate a distinct unfolded protein response (UPR) signaling pathways in two mammalian models of DM: β-TC-6 cell line and streptozotocin induced type 1 diabetes model in rats. However, a feature common to both systems was the upregulation of the GRP78 protein. Moreover, in vivo studies showed the disruption of the antioxidant system and an escalation of mitophagy against the background of a depletion of the level of ATP in pancreatic cells. In conclusion, we suggest that glucotoxic conditions induced GRP78 upregulation, and next cause depletion of the antioxidant pool and disruption of the functioning of antioxidant defense enzymes and in consequence promote mitophagy in pancreatic cells. Therefore, GRP78 may be considered as a potential therapeutic factor in patients with diabetes.