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

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.