Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress
Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have b...
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| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2014/137919 |
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| author | Liang-Jun Yan |
| author_facet | Liang-Jun Yan |
| author_sort | Liang-Jun Yan |
| collection | DOAJ |
| description | Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS) and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH), respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome. |
| format | Article |
| id | doaj-art-1b949fa224474c39a97fac62ac7d4949 |
| institution | OA Journals |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-1b949fa224474c39a97fac62ac7d49492025-08-20T02:01:50ZengWileyJournal of Diabetes Research2314-67452314-67532014-01-01201410.1155/2014/137919137919Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative StressLiang-Jun Yan0Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, RES-314E, Fort Worth, TX 76107, USAChronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS) and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH), respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.http://dx.doi.org/10.1155/2014/137919 |
| spellingShingle | Liang-Jun Yan Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress Journal of Diabetes Research |
| title | Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress |
| title_full | Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress |
| title_fullStr | Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress |
| title_full_unstemmed | Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress |
| title_short | Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress |
| title_sort | pathogenesis of chronic hyperglycemia from reductive stress to oxidative stress |
| url | http://dx.doi.org/10.1155/2014/137919 |
| work_keys_str_mv | AT liangjunyan pathogenesisofchronichyperglycemiafromreductivestresstooxidativestress |