Role of IGF-I in skeletal muscle mass maintenance

The recent identification of signaling elements that regulate skeletal muscle protein balance has provided the opportunity to determine how IGF-I alters these processes. Animal studies have revealed the important role of IGF-I in preventing muscle atrophy and enabled investigators to determine the hierarchy of signaling pathways and events within each pathway that are modulated by IGF-I. These discoveries provide opportunity for future studies to target these important signaling events and develop strategies to reverse loss of muscle mass that accompanies these catabolic states. Because there are no approved medical therapies that will reverse catabolism at present, this represents an opportunity to fulfill a major unmet medical need. The recent identification of signaling elements that regulate skeletal muscle protein balance has provided the opportunity to determine how IGF-I alters these processes. Animal studies have revealed the important role of IGF-I in preventing muscle atrophy and enabled investigators to determine the hierarchy of signaling pathways and events within each pathway that are modulated by IGF-I. These discoveries provide opportunity for future studies to target these important signaling events and develop strategies to reverse loss of muscle mass that accompanies these catabolic states. Because there are no approved medical therapies that will reverse catabolism at present, this represents an opportunity to fulfill a major unmet medical need. A serine threonine kinase that is activated in response to PI-3 kinase activation and which functions to activate mTOR and P70S6 kinase. A disease in which there is atrophy of the motor neurons leading to loss of muscle mass and strength. A general term describing the breakdown of tissue. In skeletal muscle, this process would be due to proteolysis of structural proteins, such as myosin. A group of transcription factors that activates proteins regulating muscle catabolism. AKT phosphorylates FOXO-1, leading to its exclusion from the nucleus thus inhibiting protein breakdown. A growth factor that stimulates muscle protein synthesis and inhibits protein breakdown, stimulating myoblast replication and differentiation. A growth factor with structural homology to insulin and IGF-I which binds to the same receptor but with lower affinity. A tyrosine kinase receptor that mediates the effects of IGF-I and IGF-II. Insulin receptor substrate-1. A docking protein that is phosphorylated by the IGF-I receptor and functions to activate PI-3 kinase. Similar to TNFα, this cytokine is released during inflammatory states. Cells that have entered the muscle cell lineage but are still capable of replication. Long strands of structural proteins that are grouped into bundles and form part of the contractile apparatus of muscle. During muscle cell differentiation, myoblasts fuse to form multinucleated myotubes. A component of the TORC-1 complex that can be activated by AKT or directly by cellular exposure to leucine. A ubiquitin E3 ligase that facilitates muscle protein breakdown. A ubiquitin E3 ligase whose activity is blocked by AKT inactivation of FOXO-1. Phenylalanine, unlike some other amino acids, such as leucine, has very little direct stimulatory effect on protein synthesis; therefore, its uptake and release from muscle can be used as a tool to directly measure the rates of protein synthesis in this tissue. A state is which protein accretion by tissues is stimulated and the net synthesis of protein exceeds the rate of breakdown. These are present in skeletal muscle compartments. Following injury, they replicate and differentiate into myoblasts. An enzyme that counteracts the deleterious effects of free oxygen radicals. A cytokine that is released in inflammatory states that stimulates muscle protein breakdown.