The skeletal muscle tissue has a remarkable capacity to regenerate upon injury. Recent studies have suggested that this regenerative process is improved when AMPK is activated. In the muscle of young and old mice a low calorie diet, which activates AMPK, markedly enhances muscle regeneration. Remarkably, intraperitoneal injection of AICAR, an AMPK agonist, improves the structural integrity of muscles of dystrophin-deficient mdx mice. Building on these observations we asked whether metformin, a powerful anti-hyperglycemic drug, which indirectly activates AMPK, affects the response of skeletal muscle to damage. In our conditions, metformin treatment did not significantly influence muscle regeneration. On the other hand we observed that the muscles of metformin treated mice are more resilient to cardiotoxin injury displaying lesser muscle damage. Accordingly myotubes, originated in vitro from differentiated C2C12 myoblast cell line, become more resistant to cardiotoxin damage after preincubation with metformin. Our results indicate that metformin limits cardiotoxin damage by protecting myotubes from necrosis. Although the details of the molecular mechanisms underlying the protective effect remain to be elucidated, we report a correlation between the ability of metformin to promote resistance to damage and its capacity to counteract the increment of intracellular calcium levels induced by cardiotoxin treatment. Since increased cytoplasmic calcium concentrations characterize additional muscle pathological conditions, including dystrophies, metformin treatment could prove a valuable strategy to ameliorate the conditions of patients affected by dystrophies.

Langone, F., Cannata, S., Fuoco, C., LETTIERI BARBATO, D., Testa, S., Nardozza, A.p., et al. (2014). Metformin Protects Skeletal Muscle from Cardiotoxin Induced Degeneration. PLOS ONE, 9(12), e114018 [10.1371/journal.pone.0114018].

Metformin Protects Skeletal Muscle from Cardiotoxin Induced Degeneration

CANNATA, STEFANO;FUOCO, CLAUDIA;LETTIERI BARBATO, DANIELE;NARDOZZA, AURELIO PIO;CIRIOLO, MARIA ROSA;CASTAGNOLI, LUISA;GARGIOLI, CESARE;CESARENI, GIOVANNI
2014-12-02

Abstract

The skeletal muscle tissue has a remarkable capacity to regenerate upon injury. Recent studies have suggested that this regenerative process is improved when AMPK is activated. In the muscle of young and old mice a low calorie diet, which activates AMPK, markedly enhances muscle regeneration. Remarkably, intraperitoneal injection of AICAR, an AMPK agonist, improves the structural integrity of muscles of dystrophin-deficient mdx mice. Building on these observations we asked whether metformin, a powerful anti-hyperglycemic drug, which indirectly activates AMPK, affects the response of skeletal muscle to damage. In our conditions, metformin treatment did not significantly influence muscle regeneration. On the other hand we observed that the muscles of metformin treated mice are more resilient to cardiotoxin injury displaying lesser muscle damage. Accordingly myotubes, originated in vitro from differentiated C2C12 myoblast cell line, become more resistant to cardiotoxin damage after preincubation with metformin. Our results indicate that metformin limits cardiotoxin damage by protecting myotubes from necrosis. Although the details of the molecular mechanisms underlying the protective effect remain to be elucidated, we report a correlation between the ability of metformin to promote resistance to damage and its capacity to counteract the increment of intracellular calcium levels induced by cardiotoxin treatment. Since increased cytoplasmic calcium concentrations characterize additional muscle pathological conditions, including dystrophies, metformin treatment could prove a valuable strategy to ameliorate the conditions of patients affected by dystrophies.
2-dic-2014
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/18 - GENETICA
English
Con Impact Factor ISI
Metformin; AMPK,;skeletal muscle; intracellular calcium; dystrophies
Langone, F., Cannata, S., Fuoco, C., LETTIERI BARBATO, D., Testa, S., Nardozza, A.p., et al. (2014). Metformin Protects Skeletal Muscle from Cardiotoxin Induced Degeneration. PLOS ONE, 9(12), e114018 [10.1371/journal.pone.0114018].
Langone, F; Cannata, S; Fuoco, C; LETTIERI BARBATO, D; Testa, S; Nardozza, Ap; Ciriolo, Mr; Castagnoli, L; Gargioli, C; Cesareni, G
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
Langone2014.plosone.pdf

solo utenti autorizzati

Licenza: Copyright dell'editore
Dimensione 1.96 MB
Formato Adobe PDF
1.96 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/101279
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 44
  • ???jsp.display-item.citation.isi??? 45
social impact