Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future
Twenty years have passed since Brownlee and colleagues proposed a single unifying mechanism for diabetic complications, introducing a turning point in this field of research. For the first time, reactive oxygen species (ROS) were identified as the causal link between hyperglycemia and four seemingly...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/10/5/727 |
| _version_ | 1797535201836924928 |
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| author | Carla Iacobini Martina Vitale Carlo Pesce Giuseppe Pugliese Stefano Menini |
| author_facet | Carla Iacobini Martina Vitale Carlo Pesce Giuseppe Pugliese Stefano Menini |
| author_sort | Carla Iacobini |
| collection | DOAJ |
| description | Twenty years have passed since Brownlee and colleagues proposed a single unifying mechanism for diabetic complications, introducing a turning point in this field of research. For the first time, reactive oxygen species (ROS) were identified as the causal link between hyperglycemia and four seemingly independent pathways that are involved in the pathogenesis of diabetes-associated vascular disease. Before and after this milestone in diabetes research, hundreds of articles describe a role for ROS, but the failure of clinical trials to demonstrate antioxidant benefits and some recent experimental studies showing that ROS are dispensable for the pathogenesis of diabetic complications call for time to reflect. This twenty-year journey focuses on the most relevant literature regarding the main sources of ROS generation in diabetes and their role in the pathogenesis of cell dysfunction and diabetic complications. To identify future research directions, this review discusses the evidence in favor and against oxidative stress as an initial event in the cellular biochemical abnormalities induced by hyperglycemia. It also explores possible alternative mechanisms, including carbonyl stress and the Warburg effect, linking glucose and lipid excess, mitochondrial dysfunction, and the activation of alternative pathways of glucose metabolism leading to vascular cell injury and inflammation. |
| first_indexed | 2024-03-10T11:41:11Z |
| format | Article |
| id | doaj.art-28f0c72cfcd843fd9c9b91ba75c63846 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T11:41:11Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-28f0c72cfcd843fd9c9b91ba75c638462023-11-21T18:26:36ZengMDPI AGAntioxidants2076-39212021-05-0110572710.3390/antiox10050727Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the FutureCarla Iacobini0Martina Vitale1Carlo Pesce2Giuseppe Pugliese3Stefano Menini4Department of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, ItalyDepartment of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, ItalyDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal Infantile Sciences (DINOGMI), Department of Excellence of MIUR, University of Genoa Medical School, 16132 Genoa, ItalyDepartment of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, ItalyDepartment of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, ItalyTwenty years have passed since Brownlee and colleagues proposed a single unifying mechanism for diabetic complications, introducing a turning point in this field of research. For the first time, reactive oxygen species (ROS) were identified as the causal link between hyperglycemia and four seemingly independent pathways that are involved in the pathogenesis of diabetes-associated vascular disease. Before and after this milestone in diabetes research, hundreds of articles describe a role for ROS, but the failure of clinical trials to demonstrate antioxidant benefits and some recent experimental studies showing that ROS are dispensable for the pathogenesis of diabetic complications call for time to reflect. This twenty-year journey focuses on the most relevant literature regarding the main sources of ROS generation in diabetes and their role in the pathogenesis of cell dysfunction and diabetic complications. To identify future research directions, this review discusses the evidence in favor and against oxidative stress as an initial event in the cellular biochemical abnormalities induced by hyperglycemia. It also explores possible alternative mechanisms, including carbonyl stress and the Warburg effect, linking glucose and lipid excess, mitochondrial dysfunction, and the activation of alternative pathways of glucose metabolism leading to vascular cell injury and inflammation.https://www.mdpi.com/2076-3921/10/5/727advanced glycation end-productsantioxidantsdiabeteshyperglycemiamethylglyoxalmitochondrial dysfunction |
| spellingShingle | Carla Iacobini Martina Vitale Carlo Pesce Giuseppe Pugliese Stefano Menini Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future Antioxidants advanced glycation end-products antioxidants diabetes hyperglycemia methylglyoxal mitochondrial dysfunction |
| title | Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future |
| title_full | Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future |
| title_fullStr | Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future |
| title_full_unstemmed | Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future |
| title_short | Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future |
| title_sort | diabetic complications and oxidative stress a 20 year voyage back in time and back to the future |
| topic | advanced glycation end-products antioxidants diabetes hyperglycemia methylglyoxal mitochondrial dysfunction |
| url | https://www.mdpi.com/2076-3921/10/5/727 |
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