Journal of Diabetes Investigation (Jul 2021)

Nicorandil decreases oxidative stress in slow‐ and fast‐twitch muscle fibers of diabetic rats by improving the glutathione system functioning

  • Sarai Sánchez‐Duarte,
  • Sergio Márquez‐Gamiño,
  • Rocío Montoya‐Pérez,
  • Erick Andrés Villicaña‐Gómez,
  • Karla Susana Vera‐Delgado,
  • Cipriana Caudillo‐Cisneros,
  • Fernando Sotelo‐Barroso,
  • Ma Teresa Melchor‐Moreno,
  • Elizabeth Sánchez‐Duarte

Journal volume & issue
Vol. 12, no. 7
pp. 1152 – 1161


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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 KATP channel opener, could protect slow‐ and fast‐twitch diabetic rat muscles from oxidative stress, and to unveil its possible mechanisms. 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.