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Updated: May 25, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Mitochondrial redox studies of oxidative stress in kidneys from diabetic mice
Abstract:
Chronic hyperglycemia during diabetes leads to increased production of reactive oxygen species (ROS) and increased oxidative stress (OS). Here we investigated whether changes in the metabolic state can be used as a marker of OS progression in kidneys. We examined redox states of kidneys from diabetic mice, Akita(/+) and Akita(/+);TSP1(-/-) mice (Akita mice lacking thrombospondin-1, TSP1) with increasing duration of diabetes. OS as measured by mitochondrial redox ratio (NADH/FAD) was detectable shortly after the onset of diabetes and further increased with the duration of diabetes. Thus, cryo fluorescence redox imaging was used as a quantitative marker of OS progression in kidneys from diabetic mice and demonstrated that alterations in the oxidative state of kidneys occur during the early stages of diabetes.
Insights
Diabetic kidney disease shows increased oxidative stress (OS) early on. Mitochondrial redox ratio changes serve as a marker for OS progression in diabetic kidneys.
Area of Science:
- Biochemistry
- Nephrology
- Metabolic Research
Background:
- Diabetes mellitus is characterized by chronic hyperglycemia.
- Hyperglycemia elevates reactive oxygen species (ROS) production, leading to oxidative stress (OS).
- Oxidative stress significantly contributes to diabetic kidney disease pathogenesis.
Purpose of the Study:
- To investigate if metabolic state changes can serve as a biomarker for OS progression in diabetic kidneys.
- To quantify OS in kidneys of diabetic mice using cryo fluorescence redox imaging.
- To assess the correlation between diabetes duration and kidney OS levels.
Main Methods:
- Utilized Akita and Akita;TSP1(-/-) diabetic mouse models with varying diabetes durations.
- Examined kidney redox states, specifically the mitochondrial NADH/FAD ratio.
- Employed cryo fluorescence redox imaging for quantitative OS assessment.
Main Results:
- Oxidative stress, indicated by the mitochondrial redox ratio (NADH/FAD), was detectable early in diabetes.
- OS levels progressively increased with the duration of diabetes in the examined mouse models.
- Cryo fluorescence redox imaging provided a quantitative measure of OS progression in diabetic kidneys.
Conclusions:
- Alterations in kidney oxidative state occur during the early stages of diabetes.
- Metabolic state changes, particularly the mitochondrial redox ratio, can serve as an early marker of OS progression in diabetic kidneys.
- Early detection of OS may facilitate timely interventions in diabetic kidney disease.
