Emerging role of neuregulin as a modulator of muscle metabolism

2010 ◽  
Vol 298 (4) ◽  
pp. E742-E750 ◽  
Author(s):  
Anna Gumà ◽  
Vicente Martínez-Redondo ◽  
Iliana López-Soldado ◽  
Carles Cantó ◽  
Antonio Zorzano
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Neuromuscular Junction ◽  
Muscle Contraction ◽  
Neurotrophic Factor ◽  
Muscle Metabolism ◽  
Metabolic Effects ◽  
Energetic Metabolism ◽  
Insulin Responsiveness

Neuregulin was described initially as a neurotrophic factor involved in the formation of the neuromuscular junction in skeletal muscle. However, in recent years, neuregulin has been reported to be a myokine that exerts relevant effects on myogenesis and the regulation of muscle metabolism. In this new context, the rapid and chronic metabolic effects of neuregulin appear to be related to muscle contraction. Indeed, the effects of neuregulin resemble those of exercise, which are accompanied by an improvement in insulin sensitivity. In this review, we challenge the classical role assigned to neuregulin in muscle and propound the emerging concept of its involvement in the regulation of energetic metabolism and insulin responsiveness.

scholarly journals Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism

Diabetes ◽  
2015 ◽  
Vol 64 (12) ◽  
pp. 4023-4032 ◽  
Author(s):  
Mengyao Li ◽  
Sara G. Vienberg ◽  
Olivier Bezy ◽  
Brian T. O’Neill ◽  
C. Ronald Kahn
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Muscle Metabolism ◽  
Skeletal Muscle Metabolism

scholarly journals How to Build and to Protect the Neuromuscular Junction: The Role of the Glial Cell Line-Derived Neurotrophic Factor

2020 ◽  
Vol 22 (1) ◽  
pp. 136
Author(s):  
Serena Stanga ◽  
Marina Boido ◽  
Pascal Kienlen-Campard
Keyword(s):  
Neuromuscular Junction ◽  
Muscle Contraction ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Therapeutic Potential ◽  
Muscular Atrophy ◽  
Neuromuscular Disorders ◽  
Functional Changes

The neuromuscular junction (NMJ) is at the crossroad between the nervous system (NS) and the muscle. Following neurotransmitter release from the motor neurons (MNs), muscle contraction occurs and movement is generated. Besides eliciting muscle contraction, the NMJ represents a site of chemical bidirectional interplay between nerve and muscle with the active participation of Schwann cells. Indeed, signals originating from the muscle play an important role in synapse formation, stabilization, maintenance and function, both in development and adulthood. We focus here on the contribution of the Glial cell line-Derived Neurotrophic Factor (GDNF) to these processes and to its potential role in the protection of the NMJ during neurodegeneration. Historically related to the maintenance and survival of dopaminergic neurons of the substantia nigra, GDNF also plays a fundamental role in the peripheral NS (PNS). At this level, it promotes muscle trophism and it participates to the functionality of synapses. Moreover, compared to the other neurotrophic factors, GDNF shows unique peculiarities, which make its contribution essential in neurodegenerative disorders. While describing the known structural and functional changes occurring at the NMJ during neurodegeneration, we highlight the role of GDNF in the NMJ–muscle cross-talk and we review its therapeutic potential in counteracting the degenerative process occurring in the PNS in progressive and severe diseases such as Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA). We also describe functional 3D neuromuscular co-culture systems that have been recently developed as a model for studying both NMJ formation in vitro and its involvement in neuromuscular disorders.

ALY688 elicits adiponectin-mimetic signaling and improves insulin action in skeletal muscle cells

2021 ◽  
Author(s):  
Hye Kyoung Sung ◽  
Patricia L. Mitchell ◽  
Sean Gross ◽  
Andre Marette ◽  
Gary Sweeney
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Muscle Cells ◽  
Temporal Analysis ◽  
Skeletal Muscle Cells ◽  
Adiponectin Receptor ◽  
Metabolic Effects

Adiponectin is well established to mediate many beneficial metabolic effects, and this has stimulated great interest in development and validation of adiponectin receptor agonists as pharmaceutical tools. This study investigated the effects of ALY688, a peptide-based adiponectin receptor agonist, in rat L6 skeletal muscle cells. ALY688 significantly increased phosphorylation of several adiponectin downstream effectors, including AMPK, ACC and p38MAPK, assessed by immunoblotting and immunofluorescence microscopy. Temporal analysis using cells expressing an Akt biosensor demonstrated that ALY688 enhanced insulin sensitivity. This effect was associated with increased insulin-stimulated Akt and IRS-1 phosphorylation. The functional metabolic significance of these signaling effects was examined by measuring glucose uptake in myoblasts stably overexpressing the glucose transporter GLUT4. ALY688 treatment both increased glucose uptake itself and enhanced insulin-stimulated glucose uptake. In the model of high glucose/high insulin (HGHI)-induced insulin resistant cells, both temporal studies using the Akt biosensor as well as immunoblotting assessing Akt and IRS-1 phosphorylation indicated that ALY688 significantly reduced insulin resistance. Importantly, we observed that ALY688 administration to high-fat high sucrose fed mice also improve glucose handling, validating its efficacy in vivo. In summary, these data indicate that ALY688 activates adiponectin signaling pathways in skeletal muscle, leading to improved insulin sensitivity and beneficial metabolic effects.

scholarly journals Influence of Exercise Training on Skeletal Muscle Insulin Resistance in Aging: Spotlight on Muscle Ceramides

2020 ◽  
Vol 21 (4) ◽  
pp. 1514 ◽  
Author(s):  
Paul T. Reidy ◽  
Ziad S. Mahmassani ◽  
Alec I. McKenzie ◽  
Jonathan J. Petrocelli ◽  
Scott A. Summers ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Muscle Contraction ◽  
Contractile Activity ◽  
Skeletal Muscle Insulin Resistance ◽  
Ceramide Content ◽  
Subcellular Compartmentalization ◽  
Skeletal Muscle Insulin Sensitivity

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.

scholarly journals In Vitro Effects of Emerging Bisphenols on Myocyte Differentiation and Insulin Responsiveness

2020 ◽  
Vol 178 (1) ◽  
pp. 189-200
Author(s):  
Jiongjie Jing ◽  
Yong Pu ◽  
Almudena Veiga-Lopez ◽  
Lihua Lyu
Keyword(s):  
Skeletal Muscle ◽  
Bisphenol A ◽  
Cell Lines ◽  
Glucose Transporter ◽  
Myogenic Differentiation ◽  
Metabolic Effects ◽  
C2c12 Myoblast ◽  
Short Term Exposure ◽  
Insulin Responsiveness ◽  
Myoblast Cell

Abstract Bisphenols are endocrine disrupting chemicals to which humans are ubiquitously exposed to. Prenatal bisphenol A exposure can lead to insulin resistance. However, the metabolic effects of other emerging bisphenols, such as bisphenol S (BPS) and bisphenol F (BPF), are less understood. Because the skeletal muscle is the largest of the insulin target tissues, the goal of this study was to evaluate the effects of 2 emerging bisphenols (BPS and BPF) on cytotoxicity, proliferation, myogenic differentiation, and insulin responsiveness in skeletal muscle cells. We tested this using a dose-response approach in C2C12 mouse and L6 rat myoblast cell lines. The results showed that C2C12 mouse myoblasts were more susceptible to bisphenols compared with L6 rat myoblasts. In both cell lines, bisphenol A was more cytotoxic, followed by BPF and BPS. C2C12 myoblast proliferation was higher upon BPF exposure at the 10−4 M dose and the fusion index was increased after exposure to either BPF or BPS at doses over 10−10 M. Exposure to BPS and BPF also reduced baseline expression of p-AKT (Thr) and p-GSK-3β, but not downstream effectors such as mTOR and glucose transporter-4. In conclusion, at noncytotoxic doses, BPS and BPF can alter myoblast cell proliferation, differentiation, and partially modulate early effectors of the insulin receptor signaling pathway. However, BPS or BPF short-term exposure evaluated here does not result in impaired insulin responsiveness.

scholarly journals The Role of the Four Ca Binding Sites of Troponin C in the Regulation of Skeletal Muscle Contraction

1996 ◽  
Vol 271 (14) ◽  
pp. 8381-8386 ◽  
Author(s):  
Danuta Szczesna ◽  
Georgianna Guzman ◽  
Todd Miller ◽  
Jiaju Zhao ◽  
Kamelia Farokhi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Binding Sites ◽  
Troponin C ◽  
Skeletal Muscle Contraction
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