Skip to ContentSkip to Navigation
About usNews and EventsNews articles

On the relevance of carnosine and carnosinase for the development of diabetic nephropathy

10 October 2011

PhD ceremony: Ms. E.M.S. Riedl, 14.30 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: On the relevance of carnosine and carnosinase for the development of diabetic nephropathy

Promotor(s): prof. G.J. Navis, prof. B.A. Yard

Faculty: Medical Sciences

A polymorphism in the carnosinase-1-gene (CNDP1) is associated with susceptibility to diabetic nephropathy (DN). The shortest allele, i.e. (CTG)5 (Mannheim-Allele), seems to protect homozygous diabetic patients from DN. The studies presented in this thesis were conducted to find a biological plausibility for this association.

Carnosinase-1 (CN-1) is a glycosylated protein secreted into the serum. We demonstrate that secretion of CN-1 is better when CNDP1 contains a long CTG-repeat, while (CTG)5-encoded CN-1 is poorly secreted. (CTG)5-homozygous individuals therefore have low CN-1 concentrations in serum. Besides, we found that environmental factors influence CN-1 in serum. We provide evidence that hyperglycaemia increases CN-1 secretion by enhancing N-glycosylation leading to elevated CN-1 in (CTG)5-homozygous diabetic patients with poor blood glucose control. Moreover, we show that CN-1 is inhibited by homocarnosine and seems to be present in different ion-dependent conformations.

Several studies have indicated that carnosine, the natural substrate of CN-1, might be a protective factor in DN. We demonstrated that carnosine has anti-fibrotic and cytoprotective properties. Carnosine inhibits extra-cellular-matrix accumulation, influences TGF-β-production/ -signaling and protects diabetic glomeruli from apoptosis and podocyte loss.

In conclusion, the studies described in this thesis demonstrate that CN-1 in serum is determined by the CNDP1 polymorphism. Since low CN-1 in (CTG)5-homozygous patients implicates that more protective carnosine is available, our data might explain why this allele is beneficial. The CNDP1 polymorphism might improve risk-stratification of diabetic patients. However, our data also underscore that environmental factors have to be implemented in such strategies.

Last modified:15 September 2017 3.41 p.m.
printView this page in: Nederlands

More news

  • 15 May 2019

    Academy Medal for Trudy Dehue

    Trudy Dehue, scientific sociologist, author and emeritus professor of the University of Groningen, will receive the Academy Medal from the Royal Netherlands Academy of Arts and Sciences (KNAW). The Academy Medal is awarded every other year to individuals...

  • 15 May 2019

    Van Rijn advice hits UG hard

    The advice from the Van Rijn committee concerning the funding of higher education has heavy consequences for the UG as a broad-based classical university. The proposed redistribution of funds in favour of technical sciences is at the expense of degree...

  • 14 May 2019

    Number of children with type 1 diabetes doubled

    The number of children who are annually diagnosed with type 1 diabetes has doubled over the last 30 years. This is one of the conclusions of the PhD thesis written by Angelien Spaans-Hummelink, who works as a paediatrician at the diabetes clinic at...