Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/273
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
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