Modulation of Insulin-like Growth Factor (IGF)-I and IGF-Binding Protein Interactions Enhances Skeletal Muscle Regeneration and Ameliorates the Dystrophic Pathology in mdx Mice

Schertzer, Jonathan D.; Gehrig, Stefan M.; Ryall, James G.; Lynch, Gordon S.

doi:10.2353/ajpath.2007.070292

Cited by 50 publications

(35 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The stimulation was sufficient to recruit all motor units within the contracting muscle and elicit maximum force (32), which was recorded using a Power Lab running Chart 5.0 software (AD Instruments, Castle Hill, New South Wales, Australia). Muscles were first stimulated with a series of isometric twitch contractions to determine the muscle's optimum length (L o), as described previously (48). Following a 30-min incubation at rest in the presence or absence of L-NMMA or NAC, muscles were stimulated to contract for 10 min [pulse durations: 350 ms (EDL) and 600 ms (soleus) at a frequency of 60 Hz, 12 contractions/min].…”

Section: Methodsmentioning

confidence: 99%

Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK

Merry

Steinberg

Lynch

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

110

View full text Add to dashboard Cite

Merry TL, Steinberg GR, Lynch GS, McConell GK. Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK. Am J Physiol Endocrinol Metab 298: E577-E585, 2010. First published December 15, 2009; doi:10.1152/ajpendo.00239.2009.-Reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in the regulation of skeletal muscle glucose uptake during contraction, and there is evidence that they do so via interaction with AMP-activated protein kinase (AMPK). In this study, we tested the hypothesis that ROS and NO regulate skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. Isolated extensor digitorum longus (EDL) and soleus muscles from mice that expressed a muscle-specific kinase dead AMPK␣2 isoform (AMPK-KD) and wild-type litter mates (WT) were stimulated to contract, and glucose uptake was measured in the presence or absence of the antioxidant N-acetyl-Lcysteine (NAC) or the nitric oxide synthase (NOS) inhibitor N Gmonomethyl-L-arginine (L-NMMA). Contraction increased AMPK␣2 activity in WT but not AMPK-KD EDL muscles. However, contraction increased glucose uptake in the EDL and soleus muscles of AMPK-KD and WT mice to a similar extent. In EDL muscles, NAC and L-NMMA prevented contraction-stimulated increases in oxidant levels (dichloroflourescein fluorescence) and NOS activity, respectively, and attenuated contraction-stimulated glucose uptake in both genotypes to a similar extent. In soleus muscles of AMPK-KD and WT mice, NAC prevented contraction-stimulated glucose uptake and L-NMMA had no effect. This is likely attributed to the relative lack of neuronal NOS in the soleus muscles compared with EDL muscles. Contraction increased AMPK␣ Thr 172 phosphorylation in EDL and soleus muscles of WT but not AMPK-KD mice, and this was not affected by NAC or L-NMMA treatment. In conclusion, ROS and NO are involved in regulating skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. nitric oxide; reactive oxygen species; exercise; metabolism; contraction; glucose uptake EXERCISE AND CONTRACTION INCREASE translocation of GLUT4 to the cell surface, facilitating glucose transport into skeletal muscle (55). Although the mechanism(s) by which contraction increases GLUT4 translocation and glucose uptake into skeletal muscle are not yet fully defined, there is consensus that the signals regulating this pathway are independent of the insulinsignaling pathway (31, 39). Numerous mechanisms have been implicated in regulating contraction-stimulated glucose uptake (43), and one of the most attractive and well-studied candidates is AMP-activated protein kinase (AMPK). While initial studies demonstrated that the AMPK activator 5-aminoimidazole 4-carboxamide ribonucleoside (AICAR) increased glucose uptake (17) and that increased AMPK activity during contraction correlates with glucose uptake (20, 38), disassociations between glucose uptake and contraction have also been reported (9, 34). Importantly, mice that overexpre...

show abstract

Section: Methodsmentioning

confidence: 99%

Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK

Merry

Steinberg

Lynch

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

110

View full text Add to dashboard Cite

show abstract

“…In addition, we examined the susceptibility of the diaphragm muscle to contractionmediated injury based on the protocol described by Schertzer and colleagues. 28 Briefly, muscles were length- , and 50% for Study 2), with P o determined after each lengthening contraction. The cumulated "force deficit" after contraction-mediated injury was determined by calculating the difference between P o measured 2 minutes after the lengthening contractions and P o determined before the lengthening contractions, expressed as a percentage of the P o determined before the protocol of successive lengthening contractions.…”

Section: Assessment Of Contractile Propertiesmentioning

confidence: 99%

Antibody-Directed Myostatin Inhibition Improves Diaphragm Pathology in Young but not Adult Dystrophic mdx Mice

Murphy

Ryall

Snell

et al. 2010

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle wasting and weakness, leading to premature death from respiratory and/or cardiac failure. A clinically relevant question is whether myostatin inhibition can improve function of the diaphragm, which exhibits a severe and progressive pathology comparable with that in DMD. We hypothesized that antibody-directed myostatin inhibition would improve the pathophysiology of diaphragm muscle strips from young mdx mice (when the pathology is mild) and adult mdx mice (when the pathology is quite marked). Five weeks treatment with a mouse chimera of anti-human myostatin antibody (PF-354 , 10 mg/kg/week) increased muscle mass (P < 0.05) and increased diaphragm median fiber cross-sectional area (CSA, P < 0.05) in young C57BL/10 and mdx mice , compared with salinetreated controls. PF-354 had no effect on specific force (sP o , maximum force normalized to muscle CSA) of diaphragm muscle strips from young C57BL/10 mice, but increased sP o by 84% (P < 0.05) in young mdx mice. In contrast, 8 weeks of PF-354 treatment did not improve muscle mass , median fiber CSA , collagen infiltration , or sP o of diaphragm muscle strips from adult mdx mice. PF-354 antibody-directed myostatin inhibition completely restored the functional capacity of diaphragm strips to control levels when treatment was initiated early , but not in the later stages of disease progression , suggesting that such therapies may only have a limited window of efficacy for DMD and related conditions. (Am J

show abstract

“…In the short term, if muscle mass can be increased or preserved in DMD patients, this may prolong muscle function and life expectancy. Therapeutic targets that have been investigated to stimulate muscle mass in dystrophic muscle include insulin-like growth factor-1, [17][18][19] IL-15, 20 and myostatin (MSTN). [21][22][23] MSTN, a negative regulator of muscle mass, is a member of the transforming growth factor-␤ superfamily of proteins.…”

mentioning

confidence: 99%

Targeting the Activin Type IIB Receptor to Improve Muscle Mass and Function in the mdx Mouse Model of Duchenne Muscular Dystrophy

Pistilli

Bogdanovich

Goncalves

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

The activin receptor type IIB (ActRIIB) is a transmembrane receptor for transforming growth factor-␤ superfamily members, including myostatin, that are involved in the negative regulation of skeletal muscle mass. We tested the translational hypothesis that blocking ligand binding to ActRIIB for 12 weeks would stimulate skeletal muscle growth and improve muscle function in the mdx mouse. ActRIIB was targeted using a novel inhibitor comprised of the extracellular portion of the ActRIIB fused to the Fc portion of murine IgG (sActRIIB), at concentrations of 1.0 and 10.0 mg/kg ؊1 body weight. After 12 weeks of treatment, the 10.0 mg/kg ؊1 dose caused a 27% increase in body weight with a concomitant 33% increase in lean muscle mass. Absolute force production of the extensor digitorum longus muscle ex vivo was higher in mice after treatment with either dose of sActRIIB, and the specific force was significantly higher after the lower dose (1.0 mg/kg ؊1 ), indicating functional improvement in the muscle. Circulating creatine kinase levels were significantly lower in mice treated with sActRIIB, compared with control mice. These data show that targeting the ActRIIB improves skeletal muscle mass and functional strength in the mdx mouse model of DMD, providing a therapeutic rationale for use of this molecule in treating skeletal myopathies.

show abstract

Modulation of Insulin-like Growth Factor (IGF)-I and IGF-Binding Protein Interactions Enhances Skeletal Muscle Regeneration and Ameliorates the Dystrophic Pathology in mdx Mice

Cited by 50 publications

References 43 publications

Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK

Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK

Antibody-Directed Myostatin Inhibition Improves Diaphragm Pathology in Young but not Adult Dystrophic mdx Mice

Targeting the Activin Type IIB Receptor to Improve Muscle Mass and Function in the mdx Mouse Model of Duchenne Muscular Dystrophy

Contact Info

Product

Resources

About