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Abstract: SA-PO121

High Protein Diet Accelerates Development of Diabetic Nephropathy in db/db Mice

Session Information

Category: Diabetes

  • 503 Diabetes Mellitus and Obesity: Translational


  • Nørgaard, Sisse Andersen, Novo Nordisk A/S, Måløv, Denmark
  • Sørensen, Dorte Bratbo, University of Copenhagen, Copenhagen, Denmark
  • Galsgaard, Elisabeth Douglas, Novo Nordisk A/S, Maaloev, Denmark
  • Wolfhagen Sand, Fredrik, Novo Nordisk A/S, Måløv, Denmark
  • Søndergaard, Henrik, Novo Nordisk A/S, Måløv, Denmark

Diabetic and obese db/db mice are widely used in diabetic nephropathy (DN) research. However, this model only mimics the early changes in human DN with mild albuminuria and mesangial expansion (ME) as primary readouts. Both in humans and in diabetic models, a high protein diet (HPD) has been reported to affect the progression of nephropathy. Here, the objective was to explore if a HPD could accelerate nephropathy in db/db mice with the perspectives to study more advanced aspects of DN (e.g. interstitial fibrosis) and improve the therapeutic window.


32 diabetic (C57BLKS-Leprdb/db) and 20 non-diabetic (C57BLKS-Leprdb/+) were fed either regular chow diet (21 kcal% protein) or HPD (60 kcal% protein) from 6 weeks of age (WoA) until termination at 21 WoA. In-life readouts were: body weight, blood glucose (BG), %HbA1c and albuminuria. At termination the kidneys were weighed and processed for histology and qPCR analysis. ME was scored on a scale from 0 to 3, on blinded PAS stained sections.


Feeding db/db mice HPD was well tolerated and all db/db mice were diabetic throughout the study (BG >16.6mM) although mildly reduced compared to db/db mice fed regular chow. HPD increased albuminuria more than 10-fold at 21 WoA and kidney size at termination compared to db/db mice fed regular chow. The ME score revealed a significant increase in db/db mice on HPD compared to regular chow (p<0.0001). Further histopathological assessment of renal lesions (e.g. fibrosis) and gene expression profiling of the kidney by qPCR will be performed to extend these findings.
No changes were found in db/+ mice given HPD for either of the readouts.


Feeding db/db mice HPD instead of regular chow seems to accelerate the development of diabetic nephropathy without affecting lean non-diabetic mice. Thereby, HPD could potentially improve the overall quality of this model through an accelerated disease progression and an increased therapeutic window. Further histopathological assessment of the kidney will reveal if HPD additionally enhances other readouts associated with advanced nephropathy e.g. fibrosis.


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