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

Christian Carpéné; Nathalie Boulet; Jean-Louis Grolleau; Nathalie Morin

doi:10.4239/wjd.v13.i1.37

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

World J Diabetes. 2022 Jan 15;13(1):37-53. doi: 10.4239/wjd.v13.i1.37.

Authors

Christian Carpéné¹, Nathalie Boulet², Jean-Louis Grolleau³, Nathalie Morin⁴

Affiliations

¹ Institut des Maladies Métaboliques et Cardiovasculaires, INSERM UMR1297, Toulouse 31432, France. christian.carpene@inserm.fr.
² Team Dinamix, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, Toulouse 31432, France.
³ Department of Plastic Surgery, CHU Rangueil, Toulouse 31059, France.
⁴ Faculté de Pharmacie de Paris, Université de Paris, INSERM UMR-S 1139, 3PHM, Paris 75006, France.

Abstract

Background: When combined with vanadium salts, catecholamines strongly activate glucose uptake in rat and mouse adipocytes.

Aim: To test whether catecholamines activate glucose transport in human adipocytes.

Methods: The uptake of 2-deoxyglucose (2-DG) was measured in adipocytes isolated from pieces of abdominal subcutaneous tissue removed from women undergoing reconstructive surgery. Pharmacological approaches with amine oxidase inhibitors, adrenoreceptor agonists and antioxidants were performed to unravel the mechanisms of action of noradrenaline or adrenaline (also named epinephrine).

Results: In human adipocytes, 45-min incubation with 100 µmol/L adrenaline or noradrenaline activated 2-DG uptake up to more than one-third of the maximal response to insulin. This stimulation was not reproduced with millimolar doses of dopamine or serotonin and was not enhanced by addition of vanadate to the incubation medium. Among various natural amines and adrenergic agonists tested, no other molecule was more efficient than adrenaline and noradrenaline in stimulating 2-DG uptake. The effect of the catecholamines was not impaired by pargyline and semicarbazide, contrarily to that of benzylamine or methylamine, which are recognized substrates of semicarbazide-sensitive amine oxidase. Hydrogen peroxide at 1 mmol/L activated hexose uptake but not pyrocatechol or benzoquinone, and only the former was potentiated by vanadate. Catalase and the phosphoinositide 3-kinase inhibitor wortmannin inhibited adrenaline-induced activation of 2-DG uptake.

Conclusion: High doses of catecholamines exert insulin-like actions on glucose transport in human adipocytes. At submillimolar doses, vanadium did not enhance this catecholamine activation of glucose transport. Consequently, this dismantles our previous suggestion to combine the metal ion with catecholamines to improve the benefit/risk ratio of vanadium-based antidiabetic approaches.

Keywords: Amine oxidases; Diabetes; Human adipocytes; Insulin; Obesity; Vanadium.