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
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.