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Muscle Nerve. 2015 Jul;52(1):139-42. doi: 10.1002/mus.24692. Epub 2015 May 14.

Metformin increases peroxisome proliferator-activated receptor γ Co-activator-1α and utrophin a expression in dystrophic skeletal muscle.

Author information

1
Department of Cellular and Molecular Medicine, Faculty of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.

Abstract

INTRODUCTION:

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.

KEYWORDS:

AMPK; PGC-1α; mdx mice; metformin; utrophin A

PMID:
25908446
DOI:
10.1002/mus.24692
[Indexed for MEDLINE]

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