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Updated: Nov 22, 2025

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Acute Hyperglycemia May Induce Renal Tubular Injury Through Mitophagy Inhibition
Jingyu Wang1, Xiaodan Yue1,2, Cheng Meng1
1NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Aim:
Acute hyperglycemia is closely related to kidney injury. Oxidative stress activation and notable mitochondria damages were found under acute hyperglycemia treatment in our previous work. In the present study, we explored the dose-effect relationship and the pivotal role of mitophagy in acute hyperglycemia induced tubular injuries.
Methods:
Forty non-diabetic SD rats were randomly divided and treated with different concentrations of hyperglycemia respectively during the 6-h clamp experiment. Renal morphological and functional alterations were detected. Rat renal tubular epithelial cells were treated with different concentrations of glucose for 6 h. Markers and the regulation pathway of mitophagy were analyzed.
Results:
Significant tubular injuries but not glomeruli were observed under both light and electron microscope after acute hyperglycemia treatment, which manifested as enlargement of tubular epithelial cells, disarrangement of epithelial cell labyrinths and swelling of mitochondria. Urinary microalbumin, β2-MG, CysC, NAG, GAL, and NGAL were increased significantly with the increase of blood glucose (P < 0.05). ROS was activated, mitochondrial membrane potential and LC3-II/LC3-I ratio were decreased but P62 and BNIP3L/Nix were increased in hyperglycemia groups (P < 0.05), which were reversed by AMPK activation or mTOR inhibition.
Conclusion:
Acute hyperglycemia causes obvious tubular morphological and functional injuries in a dose-dependent manner. Acute hyperglycemia could inhibit mitophagy through AMPK/mTOR pathway, which would aggravate mitochondria damage and renal tubular impairment.
Insights
Acute hyperglycemia causes dose-dependent kidney tubular injury. This occurs by inhibiting mitophagy via the AMPK/mTOR pathway, worsening mitochondrial damage and renal impairment.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Acute hyperglycemia is linked to kidney injury.
- Previous work identified oxidative stress and mitochondrial damage.
- This study investigates the dose-effect and mitophagy's role.
Purpose of the Study:
- To explore the dose-effect relationship of acute hyperglycemia on kidney injury.
- To elucidate the role of mitophagy in hyperglycemia-induced tubular damage.
- To identify the underlying molecular pathways involved.
Main Methods:
- Used a rat model with varying hyperglycemia concentrations during a 6-hour clamp.
- Assessed renal morphology and function.
- Analyzed mitophagy markers and pathways in renal tubular cells exposed to glucose.
Main Results:
- Observed dose-dependent tubular injury, not glomerular.
- Noted tubular epithelial cell enlargement and mitochondrial swelling.
- Found increased urinary biomarkers, elevated ROS, and altered mitophagy markers (LC3-II/LC3-I, P62, BNIP3L/Nix).
Conclusions:
- Acute hyperglycemia induces tubular injury in a dose-dependent manner.
- Mitophagy inhibition via the AMPK/mTOR pathway contributes to mitochondrial damage.
- This pathway exacerbates renal tubular impairment.
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