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Diabetic nephropathy in a nonobese mouse model of type 2 diabetes mellitus

Sandeep K Mallipattu1, Emily J Gallagher, Derek LeRoith

  • 1Dept. of Medicine/Nephrology, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1243, New York, NY. cijiang.he@mssm.edu.

American Journal of Physiology. Renal Physiology
|March 7, 2014
PubMed

Insights

Researchers identified a new mouse model for studying diabetic nephropathy in Type 2 diabetes mellitus (T2DM). These MKR mice exhibit key T2DM features and develop kidney disease, offering a valuable tool for research.

Area of Science:

  • Nephrology
  • Endocrinology
  • Animal Models

Background:

  • Diabetic nephropathy is a major cause of kidney failure.
  • Existing mouse models for Type 2 diabetes mellitus (T2DM) have limitations in representing human disease progression.
  • Understanding T2DM pathophysiology is crucial for developing effective treatments.

Purpose of the Study:

  • To identify and characterize a novel mouse model for studying diabetic nephropathy in the context of T2DM.
  • To evaluate the MKR mouse model for its suitability in mimicking human nonobese T2DM and its associated kidney complications.

Main Methods:

  • Utilized the MKR mouse model, characterized by functional inactivation of the insulin-like growth factor-1 receptor (IGF-1R) in skeletal muscle.
  • Induced stress in MKR mice using a high-fat diet or unilateral nephrectomy.
  • Assessed diabetic nephropathy development through albuminuria measurements and histopathological analysis.

Main Results:

  • MKR mice exhibit key features of nonobese T2DM, including insulin resistance, hyperinsulinemia, hyperglycemia, and dyslipidemia.
  • Under stress conditions, MKR mice developed progressive diabetic nephropathy, characterized by significant albuminuria.
  • Histopathological findings in MKR mice met the criteria set by the Animal Models of Diabetic Complications Consortium.

Conclusions:

  • The MKR mouse is a novel, fertile model on a common background strain suitable for studying diabetic nephropathy progression in T2DM.
  • This model effectively recapitulates key aspects of nonobese human T2DM and its renal complications.
  • The MKR model provides a valuable platform for investigating therapeutic strategies for diabetic nephropathy.
Keywords:
Type 2 diabetes mellitusdiabetic nephropathyinsulin-like growth factor-I receptorleptin

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