Role of lactate dehydrogenase A in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditions
Abstract Lactate is a cellular product of glycolytic metabolism, serving as both an additional oxidative energy substrate and a signaling molecule in metabolic regulation. Plasma lactate levels are elevated in diabetes, and chronic extracellular lactic acidosis is recognized as a negative prognostic...
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Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-98797-0 |
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| author | Audzeyenka Irena Grochowalska Klaudia Szrejder Maria Kulesza Tomasz Rachubik Patrycja Rogacka Dorota Piwkowska Agnieszka |
| author_facet | Audzeyenka Irena Grochowalska Klaudia Szrejder Maria Kulesza Tomasz Rachubik Patrycja Rogacka Dorota Piwkowska Agnieszka |
| author_sort | Audzeyenka Irena |
| collection | DOAJ |
| description | Abstract Lactate is a cellular product of glycolytic metabolism, serving as both an additional oxidative energy substrate and a signaling molecule in metabolic regulation. Plasma lactate levels are elevated in diabetes, and chronic extracellular lactic acidosis is recognized as a negative prognostic marker for the disease. The development of diabetic kidney disease is closely associated with podocyte injury, which forms a crucial layer of the glomerular filtration barrier. Given that high extracellular glucose concentrations also induce lactate production and excretion in podocytes, we hypothesize that an appropriate LDH expression pattern is crucial for maintaining proper podocyte metabolism and function. Our research shows that hyperglycemia significantly decreases lactate dehydrogenase activity in podocytes. Specifically, reduced LDHA expression under hyperglycemic conditions contributes to metabolic disturbances in these cells. Lower LDH activity results in decreased glycolytic activity, altered expression of monocarboxylate transporters, reduced insulin-dependent glucose uptake, and a decrease in the number of podocyte foot processes. These findings underscore the essential role of LDHA in the metabolic adaptation of podocytes to elevated glucose levels typical of diabetes. By elucidating the molecular mechanisms underlying podocyte injury, our study provides new insights into potential therapeutic targets for preventing or mitigating diabetic kidney disease. |
| format | Article |
| id | doaj-art-6eb4c7b26a7a4d7caefa8aec74dc7e31 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-6eb4c7b26a7a4d7caefa8aec74dc7e312025-08-20T02:20:23ZengNature PortfolioScientific Reports2045-23222025-04-0115111410.1038/s41598-025-98797-0Role of lactate dehydrogenase A in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditionsAudzeyenka Irena0Grochowalska Klaudia1Szrejder Maria2Kulesza Tomasz3Rachubik Patrycja4Rogacka Dorota5Piwkowska Agnieszka6Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of SciencesLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of SciencesLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of SciencesLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of SciencesLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of SciencesLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of SciencesLaboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of SciencesAbstract Lactate is a cellular product of glycolytic metabolism, serving as both an additional oxidative energy substrate and a signaling molecule in metabolic regulation. Plasma lactate levels are elevated in diabetes, and chronic extracellular lactic acidosis is recognized as a negative prognostic marker for the disease. The development of diabetic kidney disease is closely associated with podocyte injury, which forms a crucial layer of the glomerular filtration barrier. Given that high extracellular glucose concentrations also induce lactate production and excretion in podocytes, we hypothesize that an appropriate LDH expression pattern is crucial for maintaining proper podocyte metabolism and function. Our research shows that hyperglycemia significantly decreases lactate dehydrogenase activity in podocytes. Specifically, reduced LDHA expression under hyperglycemic conditions contributes to metabolic disturbances in these cells. Lower LDH activity results in decreased glycolytic activity, altered expression of monocarboxylate transporters, reduced insulin-dependent glucose uptake, and a decrease in the number of podocyte foot processes. These findings underscore the essential role of LDHA in the metabolic adaptation of podocytes to elevated glucose levels typical of diabetes. By elucidating the molecular mechanisms underlying podocyte injury, our study provides new insights into potential therapeutic targets for preventing or mitigating diabetic kidney disease.https://doi.org/10.1038/s41598-025-98797-0Lactate dehydrogenaseHyperglycemiaInsulinGlycolysisGlucose uptakeLactate |
| spellingShingle | Audzeyenka Irena Grochowalska Klaudia Szrejder Maria Kulesza Tomasz Rachubik Patrycja Rogacka Dorota Piwkowska Agnieszka Role of lactate dehydrogenase A in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditions Scientific Reports Lactate dehydrogenase Hyperglycemia Insulin Glycolysis Glucose uptake Lactate |
| title | Role of lactate dehydrogenase A in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditions |
| title_full | Role of lactate dehydrogenase A in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditions |
| title_fullStr | Role of lactate dehydrogenase A in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditions |
| title_full_unstemmed | Role of lactate dehydrogenase A in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditions |
| title_short | Role of lactate dehydrogenase A in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditions |
| title_sort | role of lactate dehydrogenase a in the regulation of podocyte metabolism and glucose uptake under hyperglycemic conditions |
| topic | Lactate dehydrogenase Hyperglycemia Insulin Glycolysis Glucose uptake Lactate |
| url | https://doi.org/10.1038/s41598-025-98797-0 |
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