Bone has traditionally been regarded as a static structural organ that supports movement of the body and protects the internal organs. However, evidence has been accumulated in the past decade showing that bone also functions as an endocrine organ that regulates systemic glucose and energy metabolism. Osteocalcin, an osteoblast-specific secreted protein, acts as a hormone by stimulating insulin production and increasing energy expenditure and insulin sensitivity in target organs. Animal studies have shown that an increase in the circulating concentration of osteocalcin, including via exogenous application of the protein, prevents obesity and glucose intolerance. Moreover, a number of epidemiological analyses support the role of osteocalcin in the regulation of glucose and energy homeostasis in humans. Therefore, it has been suggested that osteocalcin could be a feasible preventive or therapeutic agent for metabolic disorders. In this review, we summarize the current knowledge regarding the endocrine functions of osteocalcin and its various modes of action.
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