SSAO substrates exhibiting insulin-like effects in adipocytes as a promising treatment option for metabolic disorders

Josep Mercader, Zsuzsa Iffiú-Soltesz, Xavier Brenachot, Ágota Földi, Petra Dunkel, Balázs Balogh, Camille Attané, Philippe Valet, Péter Mátyus, Christian Carpéné

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Abstract

Background: Benzylamine exerts insulin-like effects in adipocytes (e.g., glucose uptake and antilipolysis) and improves glucose handling in rodents. Results: In murine adipocytes, benzylamine mimics another insulin action: it enhances apelin expression in a manner that is blocked by the semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) inhibitor semicarbazide. It is shown that in human adipocytes, benzylamine activates glucose transport, but its effects are not additive to maximal insulin stimulation. Benzylamine effects are hydrogen peroxide dependent. They can be reproduced by novel substrates, but not by benzaldehyde. Conclusion: Owing to the parallelism between the in vitro insulin mimicry and the in vivo improvement of glucose handling elicited by benzylamine in rodents, the SSAO/VAP-1 substrates, with stronger effects on human adipocytes than benzylamine, show promising applications for the treatment of insulin resistance.

Original languageEnglish
Pages (from-to)1735-1749
Number of pages15
JournalFuture Medicinal Chemistry
Volume2
Issue number12
DOIs
Publication statusPublished - Dec 1 2010

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

Mercader, J., Iffiú-Soltesz, Z., Brenachot, X., Földi, Á., Dunkel, P., Balogh, B., Attané, C., Valet, P., Mátyus, P., & Carpéné, C. (2010). SSAO substrates exhibiting insulin-like effects in adipocytes as a promising treatment option for metabolic disorders. Future Medicinal Chemistry, 2(12), 1735-1749. https://doi.org/10.4155/fmc.10.260