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Title: | Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of L-arginine and SOD mimic | Authors: | Stancic, Ana Filipovic, Milos Ivanovic-Burmazovic, Ivana Masovic, Sava Jankovic, Aleksandra Otasevic, Vesna Korać, Aleksandra Buzadzic, Biljana Korać, Bato |
Keywords: | Diabetes;L-Arginine;Redox regulation;Skeletal muscle;SOD mimic | Issue Date: | 25-Jun-2017 | Rank: | M22 | Project: | Reactive oxygen and nitrogen species functions in reproduction: possible pharmacological tools to treat human infertility White or/and brown: importance of adipose tissue in overall redox dependent metabolic control in physiological adaptations and metabolic disorders |
Journal: | Chemico-Biological Interactions | Abstract: | Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, L-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with L-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that L-arginine and M40403 restored diabetes-induced impairment of phospho-5′-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, L-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of L-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that L-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. |
URI: | https://biore.bio.bg.ac.rs/handle/123456789/273 | ISSN: | 0009-2797 | DOI: | 10.1016/j.cbi.2017.05.003 |
Appears in Collections: | Journal Article |
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