Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2020; 11(12): 622-643
Published online Dec 15, 2020. doi: 10.4239/wjd.v11.i12.622
Vanadium-dependent activation of glucose transport in adipocytes by catecholamines is not mediated via adrenoceptor stimulation or monoamine oxidase activity
Jessica Fontaine, Geneviève Tavernier, Nathalie Morin, Christian Carpéné
Jessica Fontaine, Geneviève Tavernier, Nathalie Morin, Christian Carpéné, Institut des Maladies Métaboliques et Cardiovasculaires, Institut National de la Santé et de la Recherche Médicale, INSERM UMR1048, Université Paul Sabatier Toulouse III, Toulouse 31432, France
Nathalie Morin, INSERM UMR 1139 Faculté de Pharmacie, Université de Paris, Paris 75006, France
Author contributions: Carpéné C designed the studies, performed the rat experiments, reviewed the literature, and wrote the manuscript; Tavernier G performed the mouse experiments, contributed to the literature review and revised the manuscript; Fontaine J isolated the cells for in vitro studies; Morin N was involved in the generation and analysis of the data.
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 which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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, Institut National de la Santé et de la Recherche Médicale, INSERM UMR1048, Université Paul Sabatier Toulouse III, CHU Rangueil, Toulouse 31432, France. christian.carpene@inserm.fr
Received: August 31, 2020
Peer-review started: August 31, 2020
First decision: October 5, 2020
Revised: October 12, 2020
Accepted: October 26, 2020
Article in press: October 26, 2020
Published online: December 15, 2020
Processing time: 103 Days and 18 Hours
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 β1-, β2- and β3-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.

Keywords: Adipocyte, Amine oxidases, Insulin, Diabetes, Vanadium, Obesity

Core Tip: In rat and mouse fat cells, the combination of catecholamines with vanadium reproduces the sugar entry activation already reported for benzylamine, methylamine or tyramine. Glucose transport stimulation is observed only with catecholamines at millimolar doses and in the presence of a vanadium dose that is ineffective on its own. The synergism between adrenaline or noradrenaline and vanadate is not mediated by adrenoceptors and resists amine oxidase inhibitors; while it is sensitive to antioxidants. Since vanadium exhibits antidiabetic properties, but with toxicological concerns, it is proposed that the combination of catecholamine derivatives plus vanadate salts might generate complexes with safer blood glucose-lowering properties.