title: Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism.
abstract: It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties.
authors.affiliation: Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Spain.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Iglesias-Osma
authors.forename: Sandy
authors.initials: S
authors.lastname: Bour
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Garcia-Barrado
authors.forename: Virgile
authors.initials: V
authors.lastname: Visentin
authors.forename: Maria Francisca
authors.initials: MF
authors.lastname: Pastor
authors.forename: Xavier
authors.initials: X
authors.lastname: Testar
authors.forename: Luc
authors.initials: L
authors.lastname: Marti
authors.forename: Gemma
authors.initials: G
authors.lastname: Enrique-Tarancon
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.forename: Julio
authors.initials: J
authors.lastname: Moratinos
authors.forename: Christian
authors.initials: C
authors.lastname: Carpéné
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D008272:Mafenide / Q000494:pharmacology*; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001596:Benzylamines; D007004:Hypoglycemic Agents; D007328:Insulin; D008744:Methylamines; D008272:Mafenide; C030796:benzylamine; D006861:Hydrogen Peroxide; C027451:methylamine; D006631:Amine Oxidase (Copper-Containing); D005947:Glucose