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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

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Alterations of urinary metabolite profile in model diabetic nephropathy

Donald F Stec1, Suwan Wang2, Cody Stothers2

  • 1Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.

Biochemical and Biophysical Research Communications
|December 16, 2014
PubMed

Insights

Diabetic mouse models with endothelial nitric oxide synthase (eNOS) deficiency can mimic human diabetic nephropathy (DN) urinary metabolite changes. These models are valuable for studying DN and developing new diagnostic methods.

Area of Science:

  • Metabolomics
  • Renal Disease Research
  • Animal Models

Background:

  • Diabetic nephropathy (DN) is a major complication of diabetes, necessitating better understanding and diagnostic tools.
  • Animal models are crucial for studying DN, but their ability to replicate human urinary metabolite changes is often limited.
  • Endothelial nitric oxide synthase (eNOS) knock-out mice exhibit renal lesions similar to human DN.

Purpose of the Study:

  • To evaluate if STZ-eNOS(-/-) and eNOS(-/-) db/db mouse models of diabetic nephropathy can reproduce urinary metabolite alterations observed in human DN.
  • To identify specific urinary metabolites that change in these diabetic mouse models.

Main Methods:

  • Utilized Type 1 (STZ-eNOS(-/-) C57BLKS) and Type 2 (eNOS(-/-) C57BLKS db/db) diabetic mouse models.
  • Analyzed urinary metabolite profiles using proton nuclear magnetic resonance (NMR) spectroscopy.
  • Correlated metabolite levels with urinary albumin-to-creatinine ratio (ACR) as a marker of renal damage.

Main Results:

  • Identified six urinary metabolites with significantly lower levels in diabetic mice compared to controls.
  • Observed major changes in metabolites related to the tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism.
  • Found that 4-hydroxyphenyl acetic acid and hippuric acid levels strongly correlated inversely with ACR, mirroring findings in human renal disease.

Conclusions:

  • STZ-eNOS(-/-) and eNOS(-/-) db/db mouse models successfully recapitulate key urinary metabolome changes seen in human diabetic nephropathy.
  • These models serve as valuable tools for future metabolomic studies in diabetic kidney disease research.
  • The findings support the utility of these models for investigating DN mechanisms and diagnostics.
Keywords:
Diabetic nephropathyMouse modelsNuclear magnetic resonanceUrinary metabolites

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