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