Human Skeletal Muscle Disuse Atrophy: Effects on Muscle Protein Synthesis, Breakdown, and Insulin Resistance—A Qualitative Review

Abstract

The ever increasing burden of an aging population and pandemic of metabolic syndrome worldwide demands further understanding of the modifiable risk factors in reducing disability and morbidity associated with these conditions. Disuse skeletal muscle atrophy (sometimes referred to as “simple” atrophy) and insulin resistance are “non-pathological” events resulting from sedentary behavior and periods of enforced immobilization e.g., due to fractures or elective orthopedic surgery. Yet, the processes and drivers regulating disuse atrophy and insulin resistance and the associated molecular events remain unclear—especially in humans. The aim of this review is to present current knowledge of relationships between muscle protein turnover, insulin resistance and muscle atrophy during disuse, principally in humans. Immobilization lowers fasted state muscle protein synthesis (MPS) and induces fed-state “anabolic resistance.” While a lack of dynamic measurements of muscle protein breakdown (MPB) precludes defining a definitive role for MPB in disuse atrophy, some proteolytic “marker” studies (e.g., MPB genes) suggest a potential early elevation. Immobilization also induces muscle insulin resistance (IR). Moreover, the trajectory of muscle atrophy appears to be accelerated in persistent IR states (e.g., Type II diabetes), suggesting IR may contribute to muscle disuse atrophy under these conditions. Nonetheless, the role of differences in insulin sensitivity across distinct muscle groups and its effects on rates of atrophy remains unclear. Multifaceted time-course studies into the collective role of insulin resistance and muscle protein turnover in the setting of disuse muscle atrophy, in humans, are needed to facilitate the development of appropriate countermeasures and efficacious rehabilitation protocols.

Muscle unloading: A comparison between spaceflight and ground‐based models

“…Skeletal muscle accounts for ≈80% of body glucose uptake after food ingestion, and diabetes mellitus is associated with reduced muscle mass, strength and power of skeletal muscle. Muscle insulin sensitivity is positively regulated by contractile activity as ≈7‐10 days of bed rest blunts the insulin‐mediated glucose uptake in human skeletal muscle .…”

“…Detailed mechanisms of disuse atrophy can be found in some excellent reviews elsewhere in the literature . Here, we present a brief overview of the mechanisms leading to disuse atrophy.…”

“…Detailed mechanisms of disuse atrophy can be found in some excellent reviews elsewhere in the literature. 154,183,184 Here, we present a brief overview of the mechanisms leading to disuse atrophy. Muscle mass is determined by the balance between muscle protein synthesis and degradation which control the accretion or loss of muscle mass (Figure 2).…”

The effect of sleep restriction, with or without high‐intensity interval exercise, on myofibrillar protein synthesis in healthy young men

“…2013; Rudrappa et al . 2016). Accordingly, a reduction in MPS, and potentially MyoPS, may underpin reductions to muscle mass induced by sleep restriction.…”

Seasonal regulation of quantal neurotransmitter release from amphibian neuromuscular junctions

“…Interestingly, the locomotor systems of dormant amphibians remain fully competent during prolonged periods of complete inactivity(Hudson & Franklin 2002a, Hudson et al 2006, Mantle et al 2009, Symonds et al 2007. This is surprising because lack of activity of vertebrate skeletal muscle typically results in muscle disuse atrophy and neuromuscular junction (NMJ) remodelling(Castro et al 1999, Lexell 1995, Phillips et al 2009, for review see(Rudrappa et al 2016, Theilen et al 2016, Tintignac et al 2015. Studying the mechanisms employed by amphibians to prevent skeletal muscle wastage and conservation of NMJ structure, our results have provided insight into the amphibian neuromuscular protective mechanism.Neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms as muscle contains molecular sensors that allow the adjustment between protein synthesis and protein breakdown(Glass 2005, Glass 2010, Ruegg & Glass 2011, Sandri 2008.…”