Insulin prevents and reverts simvastatin-induced toxicity in C2C12 skeletal muscle cells.

ABSTRACT: Simvastatin is an inhibitor of the 3-hydroxy-3-methylglutaryl-CoA reductase used for decreasing low density lipoprotein (LDL)-cholesterol in patients. It is well-tolerated but can cause myopathy. Our aims were to enlarge our knowledge regarding mechanisms and effects of insulin on simvastatin-associated myotoxicity in C2C12 myotubes. Simvastatin (10 µM) reduced membrane integrity and ATP content in myotubes treated for 24 hours, which could be prevented and partially reversed concentration- and time-dependently by insulin. Furthermore, simvastatin impaired the phosphorylation of Akt (Protein Kinase B) mainly at Ser473 and less at Thr308, indicating impaired activity of the mammalian Target of Rapamycin Complex 2 (mTORC2). Impaired activation of Akt increased mRNA expression of the muscle a

SUBMITTER: Sanvee GM 

PROVIDER: S-EPMC6520350 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature