Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l -arginine and SOD mimic
2017
Аутори:
Stančić, AnaFilipović, Miloš
Ivanović-Burmazović, Ivana
Mašović, Sava
Janković, Aleksandra
Otašević, Vesna
Korać, Aleksandra
Buzadžić, Biljana
Korać, Bato
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2017 Elsevier B.V.
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
Diabetes; Skeletal muscle; Redox regulation; L-Arginine; SOD mimicФинансирање / пројекти:
- Улога реактивних врста кисеоника и азота у репродукцији: могућа примена у лечењу хуманог стерилитета (RS-MESTD-Basic Research (BR or ON)-173054)
- Бело или/и мрко: значај масног ткива у одржању укупне редокс зависне метаболичке контроле у физиолошким адаптацијама и метаболичким поремећајима (RS-MESTD-Basic Research (BR or ON)-173055)
- European Cooperation in Science and Research (COST Action BM1203)
У:
- Chemico-Biological Interactions (2017), 272: 188-196
DOI: 10.1016/j.cbi.2017.05.003
ISSN: 0009-2797
PubMed: 28483572
WoS: 000404198300021
Scopus: 2-s2.0-85019714424
URI
http://linkinghub.elsevier.com/retrieve/pii/S0009279717300030https://radar.ibiss.bg.ac.rs/handle/123456789/2766