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MD SP12

Increased renal carnosinase (CNDP1) expression depletes CNDP1 substrates and makes renal tissue more prone to hyperglycaemia mediated damage

Supervisor (Mannheim): Bernhard Krämer
Co-Supervisor (Groningen): Harry van Goor
Graduate: Steffen Hettler

Project description

In this project we will investigate three major questions: (i) does over-expression of the human CNDP1 gene result in low renal carnosine, anserine and homocarnosine concentrations in CNDP1 transgenic BTBROb/Ob mice and is this further changed in the course of disease progression? (ii) Is carnosinasuria associated with renal function deterioration in human type 2 diabetic patients and in CNDP1 transgenic BTBROb/Ob mice? (iii) Does inhibition of carnosinase activity result in retardation of disease progression and is it still efficacious once albuminuria has developed?

References

  1. *Janssen B. et al, Diabetes. 2005; 54 (8): 2320-2327
  2. *Riedl E. et al, Diabetes 2007; 56(9):2410-2413
  3. *Zhang S. et al, PLoS One. 2016;11(1):e0146831
  4. * Zhang S. et al, Amino Acids. 2019 Jan 4
  5. *Baguet A. et al, J Appl Physiol. 2014;116(5):553-9
  6. *Dörhöfer L, DIACORE Study Group. BMC Med Genet. 2013 Feb 14;14:25.
  7. Herrera Pérez Z. et al, J Vis Exp. 2016 Mar 26;(109)
  8. *Rodriguez-Niño A. et al, Amino Acids. 2019 Jan;51(1):17-25
  9. * Qiu J. et al, Amino Acids. 2019 Jan;51(1):7-16.

* Own publications

Methods used

Mouse models (BTBRob/ob), gene-expression profiling Affymetrix/RNAseq, qPCR, Westernblotting, histology, high resolution microscopy

Collaboration Partners

  • Harry van Goor, Groningen
  • Peter Nawroth, Heidelberg
  • Jonathan Sleeman, Mannheim

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