Vol. 299, Issue 1, 96-104, October 2001

Dual Action of Octopamine on Glucose Transport into Adipocytes: Inhibition via ₃-Adrenoceptor Activation and Stimulation via Oxidation by Amine Oxidases

Virgile Visentin, Nathalie Morin, Emi Fontana, Danielle Prévot, Jeremie Boucher, Isabelle Castan, Philippe Valet, Danica Grujic and Christian Carpéné

Institut National de la Santé et de la Recherche Médicale, Toulouse, France (V.V., N.M., D.P., J.B., I.C., P.V., C.C); Department de Bioquimica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain (E.F.); and Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts (D.G.)

Octopamine, which is closely related to norepinephrine, acts as a neurotransmitter in invertebrates and is a trace amine with undefined properties in vertebrates. The octopaminergic receptors identified in insects are targets of various pesticides but are absent in vertebrates. We have established that octopamine stimulates fat cell lipolysis in mammals via activation of ₃-adrenoceptors (ARs), whereas this amine has been described elsewhere as an ₂-AR agonist and as a substrate for monoamine oxidase (MAO) or semicarbazide-sensitive amine oxidase (SSAO). Because we have recently reported that amine oxidase substrates promote glucose transport in rat and human adipocytes, the in vitro octopamine effects on lipolysis and glucose uptake were reassessed by using adipocytes from ₃-AR-deficient mice. The lipolytic effect and the counter-regulation of insulin action on glucose transport provoked by 0.1 to 1 mM octopamine or by 1 µM ₃-AR agonists found in control animals disappeared in adipocytes from ₃-AR-deficient mice. This revealed an insulin-like effect of octopamine on glucose uptake, which was dependent on its oxidation by MAO or SSAO, as was the case for tyramine and benzylamine, devoid of ₃-adrenergic agonism. Similarly, octopamine promoted glucose transport in human adipocytes and exhibited a weaker lipolytic stimulation than in rodent adipocytes. These findings indicate that, besides its lipolytic activity, octopamine exerts, at millimolar dose, dual effect on glucose transport in adipocytes: counteracting insulin action via ₃-AR activation and stimulating basal transport via its oxidation by MAO or SSAO.