Skeletal muscle is the major constituent of lean body mass and a major determinant of energy expenditure, both at rest and during physical activity. Growth hormone (GH), in turn, influences muscle mass as well as energy expenditure. GH substitution in adults increases muscle mass by 5–10%, but part of this is attributed to rehydration. In addition, GH increases resting energy expenditure independently of muscle mass, via mechanisms that may include increased conversion of the thyroid hormones thyroxine (T4) to tri-iodothyronine (T3) and stimulation of skeletal muscle blood flow. In addition, GH regulates substrate metabolism in muscle and, in particular, antagonizes insulin-stimulated glucose disposal. This effect is linked to increased free fatty acid flux, but the molecular mechanisms remain unclear. During fasting, GH-induced insulin resistance may be favourable by reducing the demand for gluconeogenesis from protein. In the postprandial phase, however, GH exposure may compromise glucose tolerance via the same mechanisms. Understanding the mechanisms by which GH antagonizes insulin-stimulated glucose disposal in muscle is an important future research field, with implications for a variety of clinical conditions ranging from malnutrition to obesity and type 2 diabetes mellitus.

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