Abstract
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 β3-adrenoceptors (ARs), whereas this amine has been described elsewhere as an α2-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 β3-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 β3-AR agonists found in control animals disappeared in adipocytes from β3-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 β3-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 β3-AR activation and stimulating basal transport via its oxidation by MAO or SSAO.
Footnotes
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This work was supported by European Union contract QLG7CT1999 00295. E.F. was partly financed by Communauté de Travail des Pyrénées and Actions Integrées PICASSO.
- Abbreviations:
- AR
- adrenergic receptor
- MAO
- monoamine oxidase
- SSAO
- semicarbazide-sensitive amine oxidase
- 2-DG
- 2-deoxyglucose
- ADA
- adenosine deaminase
- INWAT
- intra-abdominal white adipose tissue
- SCWAT
- subcutaneous white adipose tissue
- WAT
- white adipose tissue
- Received April 16, 2001.
- Accepted July 9, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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