Diabetic Hyperglycemia Induces Region-Specific Transcriptomic Remodeling in the Cochlea

Background/Objectives: Diabetes mellitus is associated with sensorineural hearing loss, but the cochlear molecular alterations related to this complication remain unclear. This pilot study aimed to characterize auditory function and region-specific transcriptomic changes in the diabetic cochlea. Methods: A streptozotocin-induced type 1 diabetic mouse model was established. Auditory function was assessed by auditory brainstem response (ABR) testing. Next-generation RNA sequencing was performed on micro-dissected cochlear regions, including the modiolus, lateral wall, and organ of Corti, followed by differential expression and gene ontology analyses. Results: STZ-induced diabetic mice showed elevated ABR thresholds compared with control mice. RNA sequencing revealed region-specific transcriptomic alterations across cochlear regions, with the lateral wall showing the greatest changes. Cross-region analysis identified a shared transcriptional signature consisting of 32 upregulated and 2 downregulated genes across the modiolus, lateral wall, and organ of Corti. Gene Ontology analysis showed enrichment of immune-related, inflammatory, metabolic stress-associated, and membrane-associated signaling. Conclusions: STZ-induced diabetes was associated with ABR threshold elevation and shared as well as region-specific cochlear transcriptomic alterations in this mouse model. These findings provide a region-specific cochlear transcriptomic resource for diabetes-associated auditory dysfunction and support future studies using larger cohorts, independent molecular validation, histological assessment, and cell-type-resolved approaches.