Osteocalcin: an endocrine link between bone and glucose metabolism.

Impaired glucose metabolism is common and contributes to the risk of diabetes and cardiovascular disease. Deletion of the gene for the osteoblast-derived protein, osteocalcin, leads to insulin resistance in mice, while the addition of osteocalcin increases insulin secretion from β-cells and adiponectin expression in adipocytes. Osteocalcin deficiency in γ-carboxyl groups, undercarboxylated osteocalcin, was found to improve insulin secretion and sensitivity in experiments. Recent studies have examined the relevance of these findings to glucose metabolism and cardiovascular risk in humans. Low total osteocalcin levels are associated with insulin resistance, diabetes and metabolic syndrome in observational studies. New therapeutic approaches to diabetes and heart disease may be anticipated if this bone-derived protein is involved in the regulation of glucose metabolism and cardiovascular risk.