Published online Dec 15, 2020. doi: 10.4239/wjd.v11.i12.622
Peer-review started: August 31, 2020
First decision: October 5, 2020
Revised: October 12, 2020
Accepted: October 26, 2020
Article in press: October 26, 2020
Published online: December 15, 2020
Processing time: 103 Days and 18 Hours
Catecholamines have been demonstrated to induce oxidative stress by generating excessive reactive oxygen species (ROS) via amine oxidase-catalyzed oxidative deamination and via autoxidation. Like other metals, vanadium has been speculated to contribute to catecholamine oxidation. While catecholamines are recognized to mobilize lipids, vanadium is known to facilitate glucose consumption in fat cells. However, the effects of the combination of catecholamines plus vanadium on glucose utilization by adipose cells require clarification.
Vanadium is a potential antidiabetic agent, the use of which is limited by toxicological issues, since several vanadate salts tend to unselectively replace phosphate in many biological reactions. The search for other forms of biological vanadium complexes with either natural compounds or with designed molecules aims at developing novel less toxic and more potent antihyperglycemic agents.
To evaluate the impact of various biogenic amines, including the catecholamines, dopamine, adrenaline and noradrenaline, without and with vanadium, on glucose transport in adipose cells. To decipher the mode of action of the synergism between amines and vanadate regarding glucose transport activation.
Research methods included animal husbandry, especially rats and mice deficient in all the β-adrenoceptor subtypes, preparations of freshly isolated adipocytes, quantitative exploration of glucose transport using uptake assays of its non-metabolizable analogue 2-deoxyglucose, together with appropriate use of pharmacological agents.
In adipose cells, we confirmed the strong stimulatory action of insulin on glucose transport, leading to a tenfold increase over baseline. This was not altered by the addition of 100 µmol/L sodium orthovanadate or clearly reproduced by any of the 25 biogenic amines tested. However, when some amines were added at millimolar doses together with vanadium, they strongly increased glucose uptake up to 70% of the maximal response to insulin. This was the case for methylamine, benzylamine and tyramine, already demonstrated elsewhere to produce hydrogen peroxide when oxidized by monoamine oxidase (MAO) or semicarbazide-sensitive amine oxidase (SSAO) highly expressed in adipocytes. In addition to these amines of reference, known to exert insulin-like effects when combined with vanadate, the catecholamines dopamine, adrenaline and noradrenaline also stimulated glucose transport in a vanadium-dependent manner. Contrarily to reference amines, the stimulation by catecholamines was resistant to MAO and SSAO inhibition. Not all the tested α- and β-adrenergic agonists displayed a clear-cut stimulation of glucose uptake, and the effects of catecholamines were not inhibited by dopaminergic or adrenergic antagonists. These latter effects were even detected in mice genetically invalidated for β-adrenergic receptors. Only antioxidants, such as ascorbate, impaired the stimulation of glucose uptake by the combination of catecholamines plus vanadate.
It is likely an interaction between vanadium and catecholamine autoxidation that generates intermediates activating in a ROS-dependent manner glucose transport in adipose cells.
The observed synergism provides the basis for possible future research of novel vanadium/amine complexes with antidiabetic properties.