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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Streptozotocin (STZ) is transported via GLUT2 into pancreatic β-cells and renal proximal tubular epithelial cells, where it induces DNA damage. Although repeated low-dose (RLD) STZ regimens are widely used to model type 1 diabetes while minimizing systemic toxicity, their direct nephrotoxicity remains underappreciated. We compared the renal and pancreatic effects of single-dose versus RLD STZ and tested whether the sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Dapa) mitigates STZ-induced tubular injury.
Male C57BL/6J mice (8–10 weeks) received vehicle, a single low dose (SLD, 50 mg/kg), a single high dose (SHD, 150 mg/kg), or RLD STZ (50 mg/kg/day for five consecutive days). For Dapa treatment, 1 mg/kg of Dapa was administered by gavage 1 h before each STZ dose. Mice were sacrificed either 24 h after the last injection or at day 14. Blood examinations, histopathological analyses, and qPCR for tubular injury and integrity markers were performed. Statistical analyses were conducted using ANOVA followed by Dunnett’s post hoc test. All procedures complied with institutional, ARRIVE, and national guidelines.
Acute phase (24 h): STZ induced proximal tubular injury, characterized by brush-border loss and reduced megalin staining, in the SHD and RLD groups. qPCR demonstrated dose-dependent upregulation of the tubular injury marker Havcr1, while proximal tubular integrity markers (Lrp2, Slc34a1, and Slc5a2) were decreased. Markers of the loop of Henle and distal tubules (Slc12a1 and Slc12a3, respectively) were unchanged, indicating that STZ injury was specific to proximal tubules. γH2AX-positive cells, reflecting DNA damage, increased in a dose-dependent manner in the cortex and were highest with RLD. Pancreatic histology showed marked islet disruption and reduced islet cell numbers after SHD, whereas RLD preserved architecture but induced islet inflammation and increased γH2AX-positive cells. With Dapa treatment, brush-border loss was attenuated, megalin expression preserved, cortical γH2AX-positive nuclei reduced, Havcr1 upregulation blunted, and Slc34a1/Slc5a2 partially restored in RLD mice. However, Dapa did not reduce islet γH2AX or alter islet cell counts.Chronic phase (day 14): The incidence of diabetes was similar among the SHD, RLD, and RLD+Dapa groups. Tubular injury and reduced tubular integrity marker expression persisted after SHD and RLD, whereas Dapa pretreatment preserved transporter expression and morphology without affecting diabetes development.
Even when systemic toxicity is limited, repeated low-dose STZ induces proximal tubule–specific DNA damage and epithelial injury with sustained loss of apical transporters. SGLT2 inhibition with dapagliflozin mitigates kidney—but not pancreatic islet—injury and does not alter diabetes incidence. Studies using STZ to model type 1 diabetes should account for direct tubular toxicity; Dapa pretreatment represents a practical strategy to minimize confounding renal injury while preserving the diabetic phenotype.
