High doses of catecholamines activate glucose transport in human adipocytes independently from adrenoceptor stimulation or vanadium addition

ARTICLE HIGHLIGHTS

Research background

We have recently reported a synergism between vanadium and catecholamines that generates a powerful activation of glucose transport in rodent adipose cells. Since the combination vanadium/adrenaline or vanadium/noradrenaline mimicked insulin activation of glucose handling in a manner depending on the production of reactive oxygen species, we proposed that further research on vanadate/catecholamine complexes could develop novel, less toxic antidiabetic therapeutic approaches for vanadium compounds.

Research motivation

To extrapolate to humans the potential antihyperglycemic properties of the vanadate/catecholamine combination found in animal models, we aimed to verify whether several amines, including adrenaline and noradrenaline, were able together with vanadate to reproduce the insulin-induced stimulation of glucose transport into human adipocytes.

Research objectives

To evaluate the impact of various biogenic amines, including the well-known catecholamines, adrenaline and noradrenaline, without and with vanadium, on glucose transport in human adipose cells.

Research methods

Preparations of freshly isolated human adipocytes, obtained from patients undergoing plastic surgery, were subjected to a pharmacological exploration of glucose transport owing to short-term uptake assays performed with the non-metabolizable radiolabeled analogue 2-deoxyglucose. An interspecies approach compared the responses of rat, mouse and human adipocytes subjected to similar stimuli.

Research results

In human adipose cells, the stimulation of glucose transport by insulin increased by two-to three times the basal uptake. Neither basal nor insulin-stimulated glucose transport was altered by 100 µmol/L sodium orthovanadate, which clearly potentiated the mild stimulatory action of hydrogen peroxide. Among fifteen biogenic amines tested, adrenaline and noradrenaline were the most efficient in activating 2-deoxyglucose uptake. The stimulation occurred within 0.01-1 mmol/L dose range and was not enhanced with vanadium. Although known to be monoamine oxidase substrates, the stimulation induced by adrenaline and noradrenaline resisted the blockade by amine oxidase inhibitors, as previously found for rodent adipocytes. The tested α- and β-adrenergic agonists did not stimulate glucose uptake in human adipocytes, and the effects of catecholamines were not inhibited by adrenergic antagonists. Benzoquinone and pyrocatechol, two of the various metabolites of catecholamine catabolism were ineffective. Only catalase, together with the antioxidant glutathione, impaired the adrenaline stimulated glucose uptake.

Research conclusions

The powerful synergism of vanadium/catecholamines previously reported on rodent adipocytes was not detectable in human fat cells. Nevertheless, adrenaline and noradrenaline were more stimulatory of hexose uptake than equivalent doses of vanadate, in a manner that was independent from adrenoceptor stimulation or amine oxidase activity.

Research perspectives

If future studies demonstrate an improvement of the antidiabetic properties of vanadium complexes via their combination with catecholamines, such improvement will likely not be the result of a synergistic effect on the glucose handling by fat cells.