Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism.
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.
Iglesias-Osma
Maria Carmen
MC
Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Spain.
Bour
Sandy
S
Garcia-Barrado
Maria Jose
MJ
Visentin
Virgile
V
Pastor
Maria Francisca
MF
Testar
Xavier
X
Marti
Luc
L
Enrique-Tarancon
Gemma
G
Valet
Philippe
P
Moratinos
Julio
J
Carpéné
Christian
C
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
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