Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2022; 13(1): 37-53
Published online Jan 15, 2022. doi: 10.4239/wjd.v13.i1.37
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
Christian Carpéné, Institut des Maladies Métaboliques et Cardiovasculaires, INSERM UMR1297, Toulouse 31432, France
Nathalie Boulet, Team Dinamix, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, Toulouse 31432, France
Jean-Louis Grolleau, Department of Plastic Surgery, CHU Rangueil, Toulouse 31059, France
Nathalie Morin, Faculté de Pharmacie de Paris, Université de Paris, INSERM UMR-S 1139, 3PHM, Paris 75006, France
Author contributions: Carpéné C designed the studies, performed the cell experiments, reviewed the literature and wrote and revised the manuscript; Grolleau JL obtained human biological resource; Boulet N isolated the cells for in vitro studies; Morin N was involved in data mining, contributed to the literature review and revised the manuscript.
Institutional review board statement: The study was approved by the I2MC Institutional Review Board: Institut des maladies métaboliques et cadiovasculaires.
Institutional animal care and use committee statement: Mice were housed and manipulated according to the INSERM guidelines and European Directive 2010/63/UE by competent and expert technicians or researchers in animal care facilities with agreement number A 31 555 04 and C 31 555 07. The experimental protocol was approved by the local ethical committee CEEA nb122.
Conflict-of-interest statement: The authors declare no competing financial interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guideline.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Christian Carpéné, PhD, Senior Researcher, Institut des Maladies Métaboliques et Cardiovasculaires, INSERM UMR1297, Université Paul Sabatier Toulouse III, CHU Rangueil, Bat L4 BP 84225, Toulouse 31432, France. christian.carpene@inserm.fr
Received: February 18, 2021
Peer-review started: February 18, 2021
First decision: April 20, 2021
Revised: April 26, 2021
Accepted: December 28, 2021
Article in press: December 28, 2021
Published online: January 15, 2022
Processing time: 326 Days and 8.5 Hours
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: Human adipocytes; Amine oxidases; Insulin; Diabetes; Vanadium; Obesity

Core Tip: Our recent results indicated that the combination of catecholamines plus vanadium strongly stimulates glucose transport in rat adipocytes. We therefore proposed that catecholamine/vanadate salts could lead to the development of novel derivatives exhibiting potent insulin-like properties. Here, we found that adrenaline and noradrenaline stimulated glucose transport in human adipocytes but in a manner that was not dependent on and not enhanced by the presence of vanadate. Consequently, our previously proposed usefulness of the synergism of catecholamines/vanadium does not work in human fat cells. This might hamper the improvement of vanadium-based antidiabetic approaches, limited so far by toxicological issues.