As the single largest organ in the body, the skeletal muscle is the major site of
insulin-stimulated
glucose uptake in the postprandial state. Skeletal muscles provide the physiological foundation for physical activities and fitness. Reduced muscle mass and strength is commonly associated with many
chronic diseases, including
obesity and
insulin resistance. The complications of diabetes on skeletal muscle mass and physiology, resulting from either
insulin deprivation or
insulin resistance, may not be life-threatening, but accelerate the lost physiological functions of
glucose homeostasis. The formation of skeletal muscle commences in the embryonic developmental stages at the time of mesoderm generation, where somites are the developmental milestone in musculoskeletal formation. Dramatic skeletal muscle growth occurs during adolescence as a result of muscle fiber
hypertrophy since muscle fiber formation is mostly completed before birth. The rate of growth rapidly decelerates in the late stages of adulthood as adipose tissue gradually accumulates more fat when energy intake exceeds expenditure. Physiologically, the key to effective
glucose homeostasis is the
hormone insulin and
insulin sensitivity of target tissues. Enhanced skeletal muscle, by either intrinsic mechanism or physical activity, offers great advantages and benefits in facilitating
glucose regulation. One key
protein factor named
myostatin is a dominant inhibitor of muscle mass. Depression of
myostatin by its propeptide or mutated receptor enhances muscle mass effectively. The muscle tissue utilizes a large portion of metabolic energy for its growth and maintenance. We demonstrated that transgenic overexpression of
myostatin propeptide in mice fed with a high-fat diet enhanced muscle mass and circulating
adiponectin, while the wild-type mice developed
obesity and
insulin resistance. Enhanced muscle growth has positive effects on fat metabolism through increasing
adiponectin expression and its regulations. Molecular studies of the exercise-induced
glucose uptake in skeletal muscle also provide insights on auxiliary substances that mimic the
plastic adaptations of muscle to exercise so that the body may amplify the effects of exercise in contending physical activity limitations or inactivity. The recent results from the
peroxisome proliferator-activated receptor γ coactivator 1α provide a promising therapeutic approach for future metabolic drug development. In summary, enhanced skeletal muscle and fundamental understanding of the biological process are critical for effective
glucose homeostasis in metabolic disorders.