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Sexual dimorphism in the progression of type 2 diabetic kidney disease in T2DN rats

Denisha R Spires1, Oleg Palygin1,2, Vladislav Levchenko1

  • 1Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Physiological Genomics
|April 19, 2021
PubMed

Insights

Diabetic kidney disease (DKD) shows sexual dimorphism. Female T2DN rats, a model for type 2 diabetes, exhibited protection against severe kidney injury compared to males.

Area of Science:

  • Nephrology
  • Endocrinology
  • Diabetology

Background:

  • Diabetic kidney disease (DKD) is a major diabetes complication, leading to renal failure and cardiovascular risks.
  • Hyperglycemia drives DKD pathologies like glomerulosclerosis and reduced filtration.
  • Emerging data reveal significant sexual dimorphism in DKD development and progression.

Purpose of the Study:

  • To investigate sexual dimorphism and renal function in T2DN rats, a nonobese model of type 2 diabetes.
  • To characterize disease progression and kidney injury development across different ages in T2DN rats.

Main Methods:

  • Utilized T2DN rats (12- and >48-wk old) and nondiabetic Wistar controls.
  • Assessed glucose tolerance, glomerular filtration rate, and kidney/glomerular injury markers.
  • Evaluated insulin resistance, plasma cholesterol, urinary nephrin, and albumin handling.

Main Results:

  • T2DN rats exhibited impaired glucose tolerance and hyperfiltration compared to controls.
  • Significant sexual dimorphism was observed in insulin resistance, cholesterol, renal/glomerular injury, and albumin handling.
  • Female T2DN rats showed protection against severe DKD development.

Conclusions:

  • T2DN rats effectively model nonobese type 2 DKD with distinct sexual dimorphism.
  • Female rats possess a protective advantage against severe diabetic kidney injury.
  • This model is valuable for studying diverse aspects of DKD pathogenesis and sex-based differences.
Keywords:
diabetic kidney diseasediabetic nephropathynonobesesex differences

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