Schematic presentation of regulation and potential actions of follistatin. Liver-derived follistatin is regulated by the glucagon-to-insulin ratio during exercise, a mechanism dependent on cAMP in hepatocytes. Circulating follistatin may interact with the endocrine pancreas to increase β-cell survival and decrease glucagon secretion during energy abundance. Circulating follistatin may also interact with skeletal muscle to induce hypertrophy or to spare the muscle from breakdown under energy deprived conditions.