On the relevance of carnosine and carnosinase for the development of diabetic nephropathy
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: | 13 March 2020 01.10 a.m. |
More news
-
06 June 2025
India-Netherlands Hydrogen Valley Fellowship Programme announced
To coincide with World Environment Day, 5 June 2025, the Indian Department of Science and Technology and the University of Groningen yesterday announced a Hydrogen Valley Fellowship Programme Partnership, allowing talented Indian scholars working on...
-
28 May 2025
Gaan avondmensen cognitief sneller achteruit dan ochtendmensen?
Wie ’s avonds opleeft en laat naar bed gaat, heeft een grotere kans op cognitieve achteruitgang dan een ochtendmens, blijkt uit UMCG-onderzoek.
-
27 May 2025
An adventure in the brain
In the exhibition Brainstorm in the University Mueseum, Iris Sommer and two other brain researchers from Groningen explain the gut-brain connection, how it was discovered that the brain does what it does, and how games motivate you to perform...