Vanadium-dependent activation of glucose transport in adipocytes by catecholamines is not mediatedviaadrenoceptor stimulation or monoamine oxidase activity

Abstract

BACKGROUND Benzylamine and methylamine activate glucose uptake in adipocytes. For tyramine, this effect has even been extended to cardiomyocytes. AIM To investigate the effects of catecholamines and other amines on glucose uptake. METHODS A screening compared 25 biogenic amines on 2-deoxyglucose (2-DG) uptake activation in rat adipocytes. Pharmacological approaches and transgenic mouse models were then used to decipher the mode of action of several hits. RESULTS In rat adipocytes, insulin stimulation of 2-DG uptake was reproduced with catecholamines. 100 µmol/L or 1 mmol/L adrenaline, noradrenaline, dopamine and deoxyepinephrine, maximally activated hexose transport only when sodium orthovanadate was added at 100 µmol/L. Such activation was similar to that already reported for benzylamine, methylamine and tyramine, well-recognized substrates of semicarbazide-sensitive amine oxidase (SSAO) and monoamine oxidase (MAO). Several, but not all, tested agonists of β-adrenoreceptors (β-ARs) also activated glucose transport while α-AR agonists were inactive. Lack of blockade by α- and β-AR antagonists indicated that catecholamine-induced 2-DG uptake was not mediated by AR stimulation. Adipocytes from mice lacking β 1 -, β 2 - and β 3 -ARs (triple KO) also responded to millimolar doses of adrenaline or noradrenaline by activating hexose transport in the presence of 100 µmol/L vanadate. The MAO blocker pargyline, and SSAO inhibitors did not block the effects of adrenaline or noradrenaline plus vanadate, which were blunted by antioxidants. CONCLUSION Catecholamines exert unexpected insulin-like actions in adipocytes when combined with vanadium. For limiting insulin resistance by activating glucose consumption at least in fat stores, we propose that catecholamine derivatives combined with vanadium can generate novel complexes that may have low toxicity and promising anti-diabetic properties.

Increased monoamine oxidase activity and imidazoline binding sites in insulin-resistant adipocytes from obese Zucker rats

“…It was immediately digested by collagenase in Krebs-Ringer buffer containing 15 mmol/L bicarbonate, 10 mmol/L HEPES, 2 mmol/L pyruvate, and 3.5% bovine serum albumin. Separation, washing, and dilution of the buoyant adipocytes were performed in the immediate continuity at 37 °C with fresh buffer prior to the functional assays, which were performed as previously described[ 20 ].…”

“…The radiolabeled non-metabolizable analog of glucose, 3 H-2-DG, was used at 0.1 mmol/L for hexose uptake assays as described previously[ 20 ], save that the assays lasted 5 min instead of 10 min for human fat cells, which are less metabolically active.…”

“…In addition to their important role in lipid mobilization, the catecholamines also activate glucose utilization in muscles[ 18 ] and in brown adipose tissue (BAT)[ 19 ]. In a recent study, we observed that high doses of catecholamines mimic the stimulatory effects of insulin on glucose transport, at least in vitro in rodent isolated adipocytes[ 20 ]. All these observations indicated that amines might constitute factors other than insulin capable of affecting directly glucose utilization in fat cells.…”

“…All these observations indicated that amines might constitute factors other than insulin capable of affecting directly glucose utilization in fat cells. More precisely, the insulin-like effect of high doses of catecholamines was independent from adrenoceptor stimulation and was rather depending on the presence of the tyrosine phosphatase inhibitor vanadium[ 20 ]. In this complex situation, we focused our comparison between lean and obese Zucker rats on the still elusive influence of amines on adipose cell biology.…”

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

“…In a recent report, we demonstrated that catecholamines such as noradrenaline and adrenaline (also named norepinephrine and epinephrine) are capable of activating glucose transport in rodent adipocytes, essentially in the presence of vanadium[ 1 ]. These observations, providing the basis for novel research of vanadium/amine complexes exhibiting antidiabetic properties of the metal ions with less toxicological issues, needed further verification.…”