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Long-term activation of semicarbazide-sensitive amine oxidase lowers circulating levels of uric acid in diabetic conditions.
MedLine Citation:
PMID:  22480418     Owner:  NLM     Status:  Publisher    
Uric acid is involved in nitrogenous waste in animals, together with ammonia and urea. Uric acid has also antioxidant properties and is a surrogate marker of metabolic syndrome. We observed that the elevated plasma uric acid of high-fat fed mice was normalized by benzylamine treatment. Indeed, benzylamine is the reference substrate of semicarbazide-sensitive amine oxidase (SSAO), an enzyme highly expressed in fat depots and vessels, which generates ammonia when catalysing oxidative deamination. Ammonia interferes with uric acid metabolism/solubility. Our aim was therefore to investigate whether the lowering action of benzylamine on uric acid was related to an improvement of diabetic complications, or was connected with SSAO-dependent ammonia production. First, we observed that benzylamine administration lowered plasma uric acid in diabetic db/db mice while it did not modify uric acid levels in normoglycemic and lean mice. In parallel, benzylamine improved the glycemic control in diabetic but not in normoglycemic mice, while plasma urea remained unaltered. Then, uric acid plasma levels were measured in mice invalidated for AOC3 gene, encoding for SSAO. These mice were unable to oxidize benzylamine but were not diabetic and exhibited unaltered plasma uric levels. Therefore, activated or abolished ammonia production by SSAO was without influence on uric acid in the context of normoglycemia. Our observations confirm that plasma uric acid increases with diabetes and can be normalized when glucose tolerance is improved. They also show that uric acid, a multifunctional metabolite at the crossroads of nitrogen waste and of antioxidant defences, can be influenced by SSAO, in a manner apparently related to changes in glucose homeostasis.
C Carpéné; A Desquesnes; A Gomez-Ruiz; Z Iffiú-Soltész; S Le Gonidec; J Mercader
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-5
Journal Detail:
Title:  Physiological research / Academia Scientiarum Bohemoslovaca     Volume:  -     ISSN:  1802-9973     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9112413     Medline TA:  Physiol Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
INSERM U1048, équipe 3, I2MC, Bat. L4, CHU Rangueil, BP 84225, Toulouse Cedex 4, France.
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