Reactive oxygen species enhance mitochondrial function, insulin sensitivity and glucose uptake in skeletal muscle of senescence accelerated prone mice SAMP8
2017
Barquissau, Valentin | Capel, Frédéric | Dardevet, Dominique | Feillet Coudray, Christine | Gallinier, Anne | Chauvin, Marie-Agnès | Rieusset, Jennifer | Morio, Béatrice | Unité de Nutrition Humaine (UNH) ; Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]) | Dynamique Musculaire et Métabolisme (DMEM) ; Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM) | STROMALab ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS) | Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT) | Institut National de la Santé et de la Recherche Médicale (INSERM) | Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT) | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN) ; Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon) ; Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM) | INRA;ANSSD;Alfediam-GSK from the French Society of Diabetes
Whereas reactive oxygen species (ROS) can have opposite impacts on insulin signaling, they have mainlybeen associated with mitochondrial dysfunction in skeletal muscle. We analyzed the relationship betweenthese three features in skeletal muscle of senescence accelerated mice (SAM) prone (P8), which arecharacterized by enhanced oxidative stress compared to SAM resistant (R1). Oxidative stress, ROSproduction, antioxidant system, mitochondrial content and functioning, as well as in vitro and in vivo insulinsignaling were investigated in gastrocnemius and quadriceps muscles. In SAMP8 compared to SAMR1,muscle content in carbonylated proteins was two-fold (p<0.01) and ROS production by xanthine oxidase70% (p<0.05) higher. Furthermore, insulin-induced Akt phosphorylation measured in vivo and ex vivo aswell as muscle glucose uptake measured ex vivo were significantly higher (p<0.05). Mitochondrialrespiration evidenced uncoupling and higher respiration rates with substrates of complexes II and IV, inagreement with higher maximal activity of complexes II and IV (+18 and 62%, respectively, p<0.05). Bycontrast, maximal activity of complex I was 22% lower (p<0.05). All strain differences were corrected after6 months of N-acetylcysteine (NAC) treatment, thus supporting the involvement of high ROS production inthese differences. In conclusion in muscle of SAMP8 compared to SAMR1, high ROS production isassociated to higher insulin sensitivity and glucose uptake but to lower mitochondrial complex I activity.These conflicting adaptations, with regards to the resulting imbalance between NADH production and use,were associated with intrinsic adjustments in the mitochondrial respiration chain (mitochondrial uncoupling,enhanced complexes II and IV activity). We propose that these bioenergetics adaptations may help atpreserving muscle metabolic flexibility of SAMP8.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
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