Colón Vázquez, JadierRosado Rivera, Nathaly M.Navedo-Jackson, Joshua J.Angueira Laureano, Arelys A.Hernández Santiago, YanitzaMaldonado-Martínez, GerónimoMéndez González, Miguel P.Eaton, Misty J.Skatchkov, Serguei N.Rivera Aponte, David E.2026-01-292026-01-292025-10-03Colón-Vázquez, J., Rosado-Rivera, N. M., Navedo-Jackson, J. J., Angueira-Laureano, A. A., Hernandez-Santiago, Y., Maldonado-Martinez, G., Méndez-González, M. P., Eaton, M. J., Skatchkov, S. N., & Rivera-Aponte, D. E. (2025). Role of Glyoxalase in Astrocytes’ Supportive Function Under Hyperglycemic Conditions: Aminoguanidine and Kir4.1 Channel Recovery. Brain Sciences, 15(10), 1075. https://doi.org/10.3390/brainsci15101072076-342510.3390/brainsci15101075https://hdl.handle.net/20.500.14352/131231This research was funded by NIH-R25GM110513 (D.E.R.-A. and M.J.E.), NIH P20 GM103475-19 (D.E.R.-A. and M.J.E.), American Diabetes Association 1-19-IBS-300 (M.J.E.), NIH-NINDS R01NS065201 (S.N.S), NIH-NINDS 2R15-NS116478-02 (S.N.S.), NIH-NINDS SC2NS124907 (M.P.M.-G., D.E.R.-A., and S.N.S.), and NIH-NIMHD G12MD007583 (UCC Core Facilities).Background/Objectives: Diabetes mellitus is a metabolic disorder, and hyperglycemia results in abnormal brain function. Since glycolysis is the main energy pathway in glial cells, astrocytes possess a more developed glyoxalase (Glo) system than neurons and exhibit better survival. Glycolysis helps to protect glia from (i) dicarbonyl stress and (ii) formation of advanced glycation end products (AGEs). Since aminoguanidine (AG) is an inhibitor of AGE production, the purpose of this study was to determine the role of AG in crucial astrocytic proteins, such as Kir4.1, Glo1, and Glo2, in hyperglycemic conditions. Methods: We cultured astrocytes in normal (5 mM)- and high (25 mM)-glucose conditions. After two weeks, we seeded the cells in six-well plates, with 300,000 cells/well, and then treated them with 9 mM of AG for 24 h. Results: Expression of the glyoxalases Glo1 and Glo2, and of Kir4.1, is decreased in hyperglycemic conditions; however, treatment with AG recovers the expression of the Kir4.1 protein as well as the inward currents of hyperglycemic astrocytes. Conclusion: We demonstrated that regulation of the glyoxalase system via AG or another scavenger of carbonyl and aldehydes containing polyamine groups can contribute to the recovery of astrocyte function in diabetic patients.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.3390/brainsci15101075https://www.mdpi.com/2076-3425/15/10/1075open access616.379-008.64616.4612.8612.015.3DiabetesAstrocytesGlyoxalase systemAminoguanidineKir4.1 channelsPotassium uptakeMembrane potentialFisiologíaEndocrinologíaNeurociencias (Biológicas)Bioquímica (Biología)3205.02 Endocrinología2411.08 Metabolismo Humano2302.19 Procesos Metabólicos2490 Neurociencias