The Role of Glycolysis in Diabetic Kidney Disease
5 affiliations
- 1Division of Nephrology, Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
- 2School of Chinese Medicine, The University of Hong Kong, Hong Kong 999000, China
- 3Department of Nephrology, Shenzhen University General Hospital, Shenzhen University, Shenzhen 518055, China
- 4State Key Laboratory of Quantitative Synthetic Biology, Center for Synthetic Biochemistry, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- 5Department of Chinese Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
Abstract
Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease worldwide and remains associated with high morbidity and mortality. In DKD, glycolytic reprogramming is triggered by hyperglycemia, hypoxia, oxidative stress, and inflammatory activation, which converge to drive metabolic imbalance. These stimuli promote excessive glycolytic flux, lactate accumulation, and diverse post-translational modifications, thereby reinforcing pathological reactions such as epithelial–mesenchymal transition, inflammation, and renal fibrosis. Accumulating evidence indicates that glycolytic alterations in DKD are highly cell type-specific. In podocytes, impaired glycolysis disrupts actin cytoskeletal integrity, promotes foot process fusion/effacement, and compromises the glomerular filtration barrier, ultimately leading to proteinuria. In tubular epithelial cells, glycolysis drives mesenchymal transformation and fibrogenesis, and engages in crosstalk with macrophages. In mesangial cells, glycolysis promotes mesangial cell hypertrophy and contributes to mesangial expansion. Mechanistically, central regulators including HIF-1α and PKM2, are modulated through glycolysis associated mechanisms, linking glycolysis to mitochondrial dysfunction, pathological cellular phenotypes, and DKD progression. Therapeutically, SGLT2 inhibitors have been clinically applied for DKD and kidney protection. Clinical studies further show that they can suppress maladaptive glycolytic activation in human metabolic analysis. Collectively, current evidence highlights glycolysis as a key driver of DKD and therapeutic targets for DKD management.
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BibTeX
@article{wang2026role,
title = {{The Role of Glycolysis in Diabetic Kidney Disease}},
author = {Yifan Wang and Xin Jiang and Liwen Cui and Yongke You and Wenjuan Zhu and Chongfei Jiang and Zhouning Liao and Jianbo Guo and Hao Lu and Baoyi Shao and Xiaozhou Luo and Pearl Pai and Haiyong Chen},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198793},
url = {https://europepmc.org/article/PMC/PMC13664804},
note = {CC BY},
}
RIS
TY - JOUR
TI - The Role of Glycolysis in Diabetic Kidney Disease
AU - Yifan Wang
AU - Xin Jiang
AU - Liwen Cui
AU - Yongke You
AU - Wenjuan Zhu
AU - Chongfei Jiang
AU - Zhouning Liao
AU - Jianbo Guo
AU - Hao Lu
AU - Baoyi Shao
AU - Xiaozhou Luo
AU - Pearl Pai
AU - Haiyong Chen
PY - 2026
DA - 2026/09/30
JO - International journal of molecular sciences
DO - 10.3390/ijms27198793
UR - https://europepmc.org/article/PMC/PMC13664804
AB - Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease worldwide and remains associated with high morbidity and mortality. In DKD, glycolytic reprogramming is triggered by hyperglycemia, hypoxia, oxidative stress, and inflammatory activation, which converge to drive metabolic imbalance. These stimuli promote excessive glycolytic flux, lactate accumulation, and diverse post-translational modifications, thereby reinforcing pathological reactions such as epithelial–mesenchymal transition, inflammation, and renal fibrosis. Accumulating evidence indicates that glycolytic alterations in DKD are highly cell type-specific. In podocytes, impaired glycolysis disrupts actin cytoskeletal integrity, promotes foot process fusion/effacement, and compromises the glomerular filtration barrier, ultimately leading to proteinuria. In tubular epithelial cells, glycolysis drives mesenchymal transformation and fibrogenesis, and engages in crosstalk with macrophages. In mesangial cells, glycolysis promotes mesangial cell hypertrophy and contributes to mesangial expansion. Mechanistically, central regulators including HIF-1α and PKM2, are modulated through glycolysis associated mechanisms, linking glycolysis to mitochondrial dysfunction, pathological cellular phenotypes, and DKD progression. Therapeutically, SGLT2 inhibitors have been clinically applied for DKD and kidney protection. Clinical studies further show that they can suppress maladaptive glycolytic activation in human metabolic analysis. Collectively, current evidence highlights glycolysis as a key driver of DKD and therapeutic targets for DKD management.
SN - 1422-0067
ER -