title: Tyramine stimulates glucose uptake in insulin-sensitive tissues in vitro and in vivo via its oxidation by amine oxidases.
abstract: Tyramine and benzylamine have been described as stimulators of glucose transport in adipocytes. This effect is dependent on amine oxidation by monoamine oxidase (MAO) or semicarbazide-sensitive amine oxidase (SSAO) and on the subsequent hydrogen peroxide formation as already demonstrated by blockade with oxidase inhibitors or antioxidants and potentiation with vanadate. In this work, we extended these observations to skeletal muscle and cardiac myocytes using in vitro and in vivo approaches. Tissue distribution studies showed that substantial extrahepatic peripheral MAO activities exist in kidney and gut, but also in insulin-sensitive tissues: heart, adipose tissue, and skeletal muscles. SSAO activity is also widely distributed and present at a lower level than MAO, except in fat depots where both oxidases were equally involved in tyramine oxidation. When tested in vitro at millimolar doses, tyramine caused a large stimulation of glucose transport in rat adipocytes and in skeletal and cardiac muscles. In vivo administration of tyramine (4 mg/kg i.p.) lowered the hyperglycemic responses to a glucose challenge in control and in streptozotocin-treated rats. This positive effect on glucose disposal was obtained without vanadate and was abolished by SSAO and MAO inhibitors. Tyramine increased hexose uptake in vivo in insulin-sensitive tissues, whereas it induced only transient effects on plasma insulin or cardiovascular parameters. In conclusion, activation of the amine oxidases present in insulin-sensitive tissues induces insulin-like effects, readily detectable in vitro, and increasing peripheral glucose utilization in vivo.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Morin
authors.forename: Virgile
authors.initials: V
authors.lastname: Visentin
authors.forename: Denis
authors.initials: D
authors.lastname: Calise
authors.forename: Luc
authors.initials: L
authors.lastname: Marti
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
authors.forename: Xavier
authors.initials: X
authors.lastname: Testar
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.forename: Yvan
authors.initials: Y
authors.lastname: Fischer
authors.forename: Christian
authors.initials: C
authors.lastname: Carpéné
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D014439:Tyramine / Q000494:pharmacology*
chemical_list: D007328:Insulin; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D005947:Glucose; D014439:Tyramine