Insights from the fructose‐derived product glucoselysine: Revisiting the polyol pathway in diabetic complications
ABSTRACT Advanced glycation end‐products (AGEs) have been extensively studied because of their close association with the onset and progression of diabetic complications. However, owing to their formation through diverse metabolic pathways, AGEs often reflect a wide range of pathological conditions...
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Wiley
2025-04-01
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| Series: | Journal of Diabetes Investigation |
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| Online Access: | https://doi.org/10.1111/jdi.70000 |
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| author | Hiroko Yamaguchi Ryoji Nagai |
| author_facet | Hiroko Yamaguchi Ryoji Nagai |
| author_sort | Hiroko Yamaguchi |
| collection | DOAJ |
| description | ABSTRACT Advanced glycation end‐products (AGEs) have been extensively studied because of their close association with the onset and progression of diabetic complications. However, owing to their formation through diverse metabolic pathways, AGEs often reflect a wide range of pathological conditions rather than being specific to diabetic complications. Consequently, identifying an AGE that directly correlates only with diabetic complications remains a challenge. Chronic hyperglycemia not only saturates the glycolytic pathway but also upregulates the polyol pathway, leading to the excessive production of fructose, a highly reactive reducing sugar. Although it has long been understood that fructose‐derived AGEs contribute to diabetic complications, their chemical structures remain unidentified. Recent breakthroughs have revealed that glucoselysine (GL) is a primary fructose‐specific AGE. Unlike other AGEs, GL is exclusively formed from fructose and not from other reducing sugars, such as glucose or galactose. This specificity provides GL with a distinct advantage in that its production pathway can be traced, making it a reliable indicator of polyol pathway activity. Furthermore, emerging evidence suggests that GL levels correlate with the progression of diabetic complications, including both micro‐ and macrovascular complications, making it a promising biomarker. GL's potential extends beyond diagnostics, as it may serve as a therapeutic target for managing complications associated with prolonged hyperglycemia and enhanced of polyol pathway. This review focuses on the enhanced polyol pathway and the formation of GL and discusses its biochemical characteristics, clinical significance, and potential as a novel diagnostic marker and therapeutic target in diabetic care. |
| format | Article |
| id | doaj-art-15d3ae32b28d4fbeb16b96699e84db95 |
| institution | DOAJ |
| issn | 2040-1116 2040-1124 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Investigation |
| spelling | doaj-art-15d3ae32b28d4fbeb16b96699e84db952025-08-20T03:07:32ZengWileyJournal of Diabetes Investigation2040-11162040-11242025-04-0116456957710.1111/jdi.70000Insights from the fructose‐derived product glucoselysine: Revisiting the polyol pathway in diabetic complicationsHiroko Yamaguchi0Ryoji Nagai1Laboratory of Food and Regulation Biology, Graduate School of Bioscience Tokai University Kumamoto JapanLaboratory of Food and Regulation Biology, Graduate School of Bioscience Tokai University Kumamoto JapanABSTRACT Advanced glycation end‐products (AGEs) have been extensively studied because of their close association with the onset and progression of diabetic complications. However, owing to their formation through diverse metabolic pathways, AGEs often reflect a wide range of pathological conditions rather than being specific to diabetic complications. Consequently, identifying an AGE that directly correlates only with diabetic complications remains a challenge. Chronic hyperglycemia not only saturates the glycolytic pathway but also upregulates the polyol pathway, leading to the excessive production of fructose, a highly reactive reducing sugar. Although it has long been understood that fructose‐derived AGEs contribute to diabetic complications, their chemical structures remain unidentified. Recent breakthroughs have revealed that glucoselysine (GL) is a primary fructose‐specific AGE. Unlike other AGEs, GL is exclusively formed from fructose and not from other reducing sugars, such as glucose or galactose. This specificity provides GL with a distinct advantage in that its production pathway can be traced, making it a reliable indicator of polyol pathway activity. Furthermore, emerging evidence suggests that GL levels correlate with the progression of diabetic complications, including both micro‐ and macrovascular complications, making it a promising biomarker. GL's potential extends beyond diagnostics, as it may serve as a therapeutic target for managing complications associated with prolonged hyperglycemia and enhanced of polyol pathway. This review focuses on the enhanced polyol pathway and the formation of GL and discusses its biochemical characteristics, clinical significance, and potential as a novel diagnostic marker and therapeutic target in diabetic care.https://doi.org/10.1111/jdi.70000Advanced glycation end‐productsDiabetic vascular complicationHyperglycemia |
| spellingShingle | Hiroko Yamaguchi Ryoji Nagai Insights from the fructose‐derived product glucoselysine: Revisiting the polyol pathway in diabetic complications Journal of Diabetes Investigation Advanced glycation end‐products Diabetic vascular complication Hyperglycemia |
| title | Insights from the fructose‐derived product glucoselysine: Revisiting the polyol pathway in diabetic complications |
| title_full | Insights from the fructose‐derived product glucoselysine: Revisiting the polyol pathway in diabetic complications |
| title_fullStr | Insights from the fructose‐derived product glucoselysine: Revisiting the polyol pathway in diabetic complications |
| title_full_unstemmed | Insights from the fructose‐derived product glucoselysine: Revisiting the polyol pathway in diabetic complications |
| title_short | Insights from the fructose‐derived product glucoselysine: Revisiting the polyol pathway in diabetic complications |
| title_sort | insights from the fructose derived product glucoselysine revisiting the polyol pathway in diabetic complications |
| topic | Advanced glycation end‐products Diabetic vascular complication Hyperglycemia |
| url | https://doi.org/10.1111/jdi.70000 |
| work_keys_str_mv | AT hirokoyamaguchi insightsfromthefructosederivedproductglucoselysinerevisitingthepolyolpathwayindiabeticcomplications AT ryojinagai insightsfromthefructosederivedproductglucoselysinerevisitingthepolyolpathwayindiabeticcomplications |