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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 beta3-adrenoceptors (ARs), whereas this amine has been described elsewhere as an alpha2-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 beta3-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 microM beta3-AR agonists found in control animals disappeared in adipocytes from beta3-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 beta3-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 beta3-AR activation and stimulating basal transport via its oxidation by MAO or SSAO.

Semicarbazide-sensitive amine oxidases (SSAO) are widely distributed enzymes scavenging biogenic or exogenous amines and generating hydrogen peroxide. We asked whether human adipose tissue could express SSAO. Since hydrogen peroxide exhibits pharmacological insulin-like effects, we also tested whether its endogenous production by SSAO could mimic several insulin effects on adipocytes, such as stimulation of glucose uptake and inhibition of lipolysis. The benzylamine oxidation by human adipose tissue was inhibited by semicarbazide or hydralazine and resistant to pargyline or selegiline. It was due to an SSAO activity localized in adipocyte membranes. A protein of 100-kDa and a 4-kb mRNA corresponding to SSAO were identified in either mammary or abdominal subcutaneous fat depots. In isolated adipocytes, SSAO oxidized similarly benzylamine and methylamine that dose dependently stimulated glucose transport in a semicarbazide-sensitive manner. Antioxidants also inhibited the benzylamine and methylamine effects. Moreover, the ability of diverse substrates to be oxidized by adipocytes was correlated to their effect on glucose transport. Benzylamine and methylamine exerted antilipolytic effects with a maximum attained at 1 mM. These results show that human adipocytes express a membrane-bound SSAO that not only readily oxidizes exogenous amines and generates H(2)O(2), but that also interplays with glucose and lipid metabolism by exerting insulin-like actions. Based on these results and the fact that variations in plasma levels of the soluble form of SSAO have been previously reported in diabetes, we propose that determination of adipocyte SSAO, feasible on subcutaneous microbiopsies, could bring relevant information in pathologies such as obesity or diabetes.