{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:38:57Z","timestamp":1790095137473,"version":"4.0.1"},"reference-count":25,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pisa University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic retinopathy (DR), traditionally considered a microvascular complication, is now recognized as a neuroinflammatory disorder involving retinal glial cells. Aldose reductase (AKR1B1), a key enzyme in the polyol pathway, has been implicated in the hyperglycemia-induced inflammatory response in various cell types, although its role in retinal M\u00fcller glial cells under acute glucose stress remains unclear. This study investigates AKR1B1 activity and its contribution to inflammatory signaling in MIO-M1 human M\u00fcller cells exposed to acute hyperglycemia. AKR1B1 expression and activity, as well as NF-\u03baB activation and COX-2 expression, were evaluated. Sorbinil, a specific AKR1B1 inhibitor, was used to determine the enzyme\u2019s contribution to acute hyperglycemia-induced inflammation. Acute high-glucose treatment significantly increased AKR1B1 activity and sorbitol accumulation without affecting cell viability. In addition, activation of NF-\u03baB and increased expression of cyclooxygenase-2 (COX-2) were observed, both of which were significantly reduced by Sorbinil. Our findings highlight the role of macroglia as active contributors to early inflammatory events in DR and suggest that transient hyperglycemic spikes are sufficient to trigger AKR1B1-dependent glial activation.<\/jats:p>","DOI":"10.3390\/ijms26146741","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:45:52Z","timestamp":1752572752000},"page":"6741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Acute Hyperglycemia-Induced Inflammation in MIO-M1 Cells: The Role of Aldose Reductase"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-2228","authenticated-orcid":false,"given":"Francesca","family":"Felice","sequence":"first","affiliation":[{"name":"Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutrafood \u201cNutraceuticals and Food for Health\u201d, University of Pisa, 56124 Pisa, Italy"},{"name":"Center for Instrument Sharing University of Pisa (CISUP), Lungarno Pacinotti, 43\/44, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-0496","authenticated-orcid":false,"given":"Gemma","family":"Sardelli","sequence":"additional","affiliation":[{"name":"National Research Council\u2014CNR, Institute on Clinical Physiology, via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Balestri","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutrafood \u201cNutraceuticals and Food for Health\u201d, University of Pisa, 56124 Pisa, Italy"},{"name":"Center for Instrument Sharing University of Pisa (CISUP), Lungarno Pacinotti, 43\/44, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Piazza","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy"},{"name":"National Research Council\u2014CNR, Institute on Clinical Physiology, via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8864-5043","authenticated-orcid":false,"given":"Mario","family":"Cappiello","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutrafood \u201cNutraceuticals and Food for Health\u201d, University of Pisa, 56124 Pisa, Italy"},{"name":"Center for Instrument Sharing University of Pisa (CISUP), Lungarno Pacinotti, 43\/44, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Mosca","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3165-6128","authenticated-orcid":false,"given":"Antonella","family":"Del Corso","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutrafood \u201cNutraceuticals and Food for Health\u201d, University of Pisa, 56124 Pisa, Italy"},{"name":"Center for Instrument Sharing University of Pisa (CISUP), Lungarno Pacinotti, 43\/44, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6326-2897","authenticated-orcid":false,"given":"Martina","family":"Avanatti","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7005-654X","authenticated-orcid":false,"given":"Simone","family":"Allegrini","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutrafood \u201cNutraceuticals and Food for Health\u201d, University of Pisa, 56124 Pisa, Italy"},{"name":"Center for Instrument Sharing University of Pisa (CISUP), Lungarno Pacinotti, 43\/44, 56126 Pisa, 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