Glucocorticoids exert their impact on metabolism through several different tissues in the body. In the presence of glucocorticoids there is an increase in adiposity as well as an increase in lipolysis, leading to elevated free fatty acids in the circulation and an increase in insulin resistance. Muscle undergoes proteolysis, releasing amino acids that increase insulin resistance. Postreceptor insulin signaling defects such as a decrease in IRS-1 also contribute to insulin resistance. In the liver, there is increased steatosis, causing insulin resistance, which is compounded by increased gluconeogenesis and hyperglycemia. The bone is the site of osteocalcin production, driven by the IR. Osteocalcin normally participates in bone turnover as well as suppresses increases in adiposity and steatosis. These actions are inhibited by glucocorticoids.