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.
Acknowledgements
The authors express gratitude to D Prévot, S Grès, D Daviaud and E Wanecq for technical help, to the staff of plastic surgery of Rangueil hospital (Toulouse) for facilitating acces to surgically removed excess fat deposits and to the staff of animal unit of I2MR, Toulouse, for invaluable help. The expertise of P Valet regarding apelin biology and the invaluable assistance of P Tapolcsányi and É.Tóth-Sarudy in chemical synthesis and purification, are gratefully acknowledged. This work was partly supported by the “Communauté de Travail des Pyrénées” (mini-network: http://obesitydiabetesinctp.weebly.com), the DIOMED project (SUDOE 1/P1/E178), and by the “Partenariat Balaton” (bilateral project between Egide and Hungarian National Office of Research and Technology for 2007/08 and 2010/11), which made possible the Franco-Spanish and Franco-Hungarian exchanges, respectively.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.