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This study investigated how various glucose concentrations influence SC viability, oxidative stress, and autophagy, which contribute to diabetic neuropathy. RSC96 SCs were cultured under five glucose conditions (0, 2.5, 5.5, 50, or 100\u2009mM) for 24, 48, and 72\u2009h. Cell viability was assessed by MTT; ROS levels were determined by DCFDA staining, and apoptosis and ER stress markers, as well as autophagy\u2010related proteins were assessed by Western blotting. Autophagic flux was also analyzed using bafilomycin A1 and Cyto\u2010ID. The results revealed time\u2010dependent increases in cell death across all glucose conditions, especially under deprivation and low glucose (LG) conditions. ROS, CHOP, Bax, and cleaved caspase\u20103 levels increased from 24 to 72\u2009h. The initial increase in the LC3B\u2010II\/I ratio indicated that autophagy was overactivated under glucose deprivation or LG conditions but impaired by 72\u2009h, as indicated by reduced Lamp\u20102 expression. High glucose conditions led to early and persistent autophagy suppression, with minimal autophagic flux and vacuole formation. These findings demonstrate that SCs are sensitive to glucose levels and undergo distinct autophagic impairments through different mechanisms under persistent low or high glucose environments.<\/jats:p>","DOI":"10.1002\/kjm2.70145","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T17:40:37Z","timestamp":1765647637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lysosome Evanescence Mediates Autophagic Flux Impairment in Glucose Imbalanced Environments"],"prefix":"10.1002","volume":"42","author":[{"given":"Yuan\u2010Chen","family":"Cheng","sequence":"first","affiliation":[{"name":"Postgraduate Year Residency, Department of Medical Education, Chang Gung Memorial Hospital\u2010Kaohsiung Medical Center Chang Gung University College of Medicine  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010Li","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Microbiology and Immunology, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Chang Gung Memorial Hospital\u2010Kaohsiung Medical Center Chang Gung University College of Medicine  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9487-9025","authenticated-orcid":false,"given":"Wei\u2010Chun","family":"Hung","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Microbiology and Immunology, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Hua","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Postgraduate Year Residency, Department of Medical Education, Chang Gung Memorial Hospital\u2010Kaohsiung Medical Center Chang Gung University College of Medicine  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-0562","authenticated-orcid":false,"given":"Yi\u2010Hsuan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang\u2010I","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Anesthesiology Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.05.003"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17446651.2022.2079495"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/nlme.2000.3976"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03021-8"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4593052"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105952"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1427679"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2021.0135"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1824-6"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2018.11.004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.06.010"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02175-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20950-9"},{"issue":"3","key":"e_1_2_10_15_1","first-page":"25","article-title":"Melatonin Ameliorates High Glucose\u2010Induced Autophagy in Schwann Cells","volume":"14","author":"Salem H. 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