title: Metformin increases peroxisome proliferator-activated receptor γ Co-activator-1α and utrophin a expression in dystrophic skeletal muscle.
abstract: BACKGROUND
  Metformin (MET) stimulates skeletal muscle AMP-activated protein kinase (AMPK), a key phenotype remodeling protein with emerging therapeutic relevance for Duchenne muscular dystrophy (DMD). Our aim was to identify the mechanism of impact of MET on dystrophic muscle.
  
  
  METHODS
  We investigated the effects of MET in cultured C2 C12 muscle cells and mdx mouse skeletal muscle. Expression of potent phenotypic modifiers was assessed, including peroxisome proliferator-activated receptor (PPAR)γ coactivator-1α (PGC-1α), PPARδ, and receptor-interacting protein 140 (RIP140), as well as that of the dystrophin-homolog, utrophin A.
  
  
  RESULTS
  In C2 C12 cells, MET augmented expression of PGC-1α, PPARδ, and utrophin A, whereas RIP140 content was reciprocally downregulated. MET treatment of mdx mice increased PGC-1α and utrophin A and normalized RIP140 levels.
  
  
  CONCLUSIONS
  In this study we identify the impact of MET on skeletal muscle and underscore the timeliness and importance of investigating MET and other AMPK activators as relevant therapeutics for DMD.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ljubicic
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Jasmin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D018101:Mice, Inbred mdx; D032342:Muscle Cells / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000473:pathology*; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D049411:Utrophin / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D049411:Utrophin; D008687:Metformin
keywords: AMPK; PGC-1α; mdx mice; metformin; utrophin A