Article ; Online: Nicorandil decreases oxidative stress in slow- and fast-twitch muscle fibers of diabetic rats by improving the glutathione system functioning.
Journal of diabetes investigation
2021 Volume 12, Issue 7, Page(s) 1152–1161
Abstract: Aims/introduction: Myopathy is a common complication of any diabetes type, consisting in failure to preserve mass and muscular function. Oxidative stress has been considered one of the main causes for this condition. This study aimed to search if ... ...
| Abstract | Aims/introduction: Myopathy is a common complication of any diabetes type, consisting in failure to preserve mass and muscular function. Oxidative stress has been considered one of the main causes for this condition. This study aimed to search if Nicorandil, a K Materials and methods: Diabetes was induced in male Wistar rats by applying intraperitoneally streptozotocin (STZ) at 100 mg/kg doses. Nicorandil (3 mg/kg/day) was administered along 4 weeks. An insulin tolerance test and assessment of fasting blood glucose (FBG), TBARS, reduced (GSH), and disulfide (GSSG) glutathione levels, GSH/GSSG ratio, and mRNA expression of glutathione metabolism-related genes were performed at end of treatment in soleus and gastrocnemius muscles. Results: Nicorandil significantly reduced FBG levels and enhanced insulin tolerance in diabetic rats. In gastrocnemius and soleus muscles, Nicorandil attenuated the oxidative stress by decreasing lipid peroxidation (TBARS), increasing total glutathione and modulating GPX1-mRNA expression in both muscle's types. Nicorandil also increased GSH and GSH/GSSG ratio and downregulated the GCLC- and GSR-mRNA in gastrocnemius, without significative effect on those enzymes' mRNA expression in diabetic soleus muscle. Conclusions: In diabetic rats, Nicorandil attenuates oxidative stress in slow- and fast-twitch skeletal muscles by improving the glutathione system functioning. The underlying mechanisms for the modulation of glutathione redox state and the transcriptional expression of glutathione metabolism-related genes seem to be fiber type-dependent. |
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| MeSH term(s) | Animals ; Diabetes Mellitus, Experimental/drug therapy ; Gene Expression Regulation/drug effects ; Glutathione/drug effects ; Lipid Peroxidation/drug effects ; Male ; Muscle Fibers, Fast-Twitch/drug effects ; Muscle Fibers, Slow-Twitch/drug effects ; Muscle, Skeletal/drug effects ; Nicorandil/pharmacology ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Rats ; Rats, Wistar ; Streptozocin ; Transcription, Genetic/drug effects | |||||
| Chemical Substances | Nicorandil (260456HAM0) ; Streptozocin (5W494URQ81) ; Glutathione (GAN16C9B8O) | |||||
| Language | English | |||||
| Publishing date | 2021-02-20 | |||||
| Publishing country | Japan | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 2625840-7 | |||||
| ISSN | 2040-1124 ; 2040-1116 | |||||
| ISSN (online) | 2040-1124 | |||||
| ISSN | 2040-1116 | |||||
| DOI | 10.1111/jdi.13513 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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