ArticleJournal of the American Society of Nephrology : JASN2014
Endogenous fructose production and fructokinase activation mediate renal injury in diabetic nephropathy.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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96 citing papers in PubMed, 162 citations in OpenAlex.
- Mitigation of renal tubular injury by SIRT6 may improve individual outcomes in diabetic kidney disease-potential mechanisms involving epigenetic repression of inflammatory responses.Journal of advanced research · 2026Article
- Fructose: metabolic signal and modern hazard.Nature metabolism · 2026Review
- The association between high fructose corn syrup and the development of type-2 diabetes.Frontiers in clinical diabetes and healthcare · 2026Review
- Vitamin D deficiency and metabolic disorders increase albuminuria risk in type 2 diabetes (ACR 0.1-300 mg/g): a nomogram-based stratification.Frontiers in endocrinology · 2026Article
- Metabolic and Vascular Inflammation in Alopecia Areata: Linking Uric Acid, Lipid Imbalance and ICAM-1 Upregulation.Experimental dermatology · 2025Article
- Association between serum osmolality and chronic kidney disease prevalence: Evidence from NHANES 1999-2018.Scientific reports · 2025Article
- Fructose metabolism and its roles in metabolic diseases, inflammatory diseases, and cancer.Molecular biomedicine · 2025Review
- Do microglia metabolize fructose in Alzheimer's disease?Journal of neuroinflammation · 2025Review
- Handling the sugar rush: the role of the renal proximal tubule.American journal of physiology. Renal physiology · 2024Review
- Pregnancy Metabolic Adaptation and Changes in Placental Metabolism in Preeclampsia.Geburtshilfe und Frauenheilkunde · 2024Article
- Nutrient quality in dietary therapy for diabetes and diabetic kidney disease.Journal of diabetes investigation · 2024Review
- High incidence of sebaceous gland inflammation in aldose reductase-deficient mice.Chemico-biological interactions · 2024Article
- Anti-inflammatory mechanism of the non-volatile ingredients originated from Guanghuoxiang () based on high performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope and cell metabolomics.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Profiling Cell Heterogeneity and Fructose Transporter Expression in the Rat Nephron by Integrating Single-Cell and Microdissected Tubule Segment Transcriptomes.International journal of molecular sciences · 2024Article
- Molecular Challenges and Opportunities in Climate Change-Induced Kidney Diseases.Biomolecules · 2024Review
- The Intersection of Genetic Factors, Aberrant Nutrient Metabolism and Oxidative Stress in the Progression of Cardiometabolic Disease.Antioxidants (Basel, Switzerland) · 2024Review
- MAPK1 Mediates MAM Disruption and Mitochondrial Dysfunction in Diabetic Kidney Disease via the PACS-2-Dependent Mechanism.International journal of biological sciences · 2024Article
- Ketohexokinase-dependent metabolism of cerebral endogenous fructose in microglia drives diabetes-associated cognitive dysfunction.Experimental & molecular medicine · 2023Article
- Endogenous Fructose Production and Metabolism Drive Metabolic Dysregulation and Liver Disease in Mice with Hereditary Fructose Intolerance.Nutrients · 2023Article
- The fructose survival hypothesis for obesity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
36 more citing papers are in PubMed but not listed here.
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26 authors at 8 institutions in 5 countries.
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Abstract
Diabetes is associated with activation of the polyol pathway, in which glucose is converted to sorbitol by aldose reductase. Previous studies focused on the role of sorbitol in mediating diabetic complications. However, in the proximal tubule, sorbitol can be converted to fructose, which is then metabolized largely by fructokinase, also known as ketohexokinase, leading to ATP depletion, proinflammatory cytokine expression, and oxidative stress. We and others recently identified a potential deleterious role of dietary fructose in the generation of tubulointerstitial injury and the acceleration of CKD. In this study, we investigated the potential role of endogenous fructose production, as opposed to dietary fructose, and its metabolism through fructokinase in the development of diabetic nephropathy. Wild-type mice with streptozotocin-induced diabetes developed proteinuria, reduced GFR, and renal glomerular and proximal tubular injury. Increased renal expression of aldose reductase; elevated levels of renal sorbitol, fructose, and uric acid; and low levels of ATP confirmed activation of the fructokinase pathway. Furthermore, renal expression of inflammatory cytokines with macrophage infiltration was prominent. In contrast, diabetic fructokinase-deficient mice demonstrated significantly less proteinuria, renal dysfunction, renal injury, and inflammation. These studies identify fructokinase as a novel mediator of diabetic nephropathy and document a novel role for endogenous fructose production, or fructoneogenesis, in driving renal disease.
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