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

作　　者：Jessica Fontaine Geneviève Tavernier Nathalie Morin Christian Carpéné 

机构地区：[1]Institut des Maladies Métaboliques et Cardiovasculaires,Institut National de la Santéet de la Recherche Médicale,INSERM UMR1048,UniversitéPaul Sabatier Toulouse III,Toulouse 31432,France [2]INSERM UMR 1139 Facultéde Pharmacie,Universitéde Paris,Paris 75006,France

出　　处：《World Journal of Diabetes》2020年第12期622-643,共22页世界糖尿病杂志（英文版）（电子版）

基　　金：We thank the staff of animal unit CREFRE, currently headed by Xavier Collet, andespecially its Rangueil satellite for housing wild type and transgenic rodents, andAnne Bouloumié for helpful discussions.

摘　　要：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.100μmol/L or 1 mmol/L adrenaline,noradrenaline,dopamine and deoxyepinephrine,maximally activated hexose transport only when sodium orthovanadate was added at 100μmol/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 ofβ-adrenoreceptors(β-ARs)also activated glucose transport whileα-AR agonists were inactive.Lack of blockade byα-andβ-AR antagonists indicated that catecholamine-induced 2-DG uptake was not mediated by AR stimulation.Adipocytes from mice lackingβ1-,β2-andβ3-ARs(triple KO)also responded to millimolar doses of adrenaline or noradrenaline by activating hexose transport in the presence of 100μmol/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.

关 键 词：ADIPOCYTE Amine oxidases INSULIN Diabetes VANADIUM Obesity 

分 类 号：R965[医药卫生—药理学]