The complexity of the metabolic syndrome and insulin resistance is highlighted by recent findings that the vitamin K dependent protein osteocalcin, is involved in energy metabolism, adiposity and glucose homeostasis. Bone tissue may play a role in glucose metabolism because it is an endocrine gland and responds to insulin with differentiation of osteoblasts and the release of insulin like growth factor I. Administration of exogenous osteocalcin to osteocalcin deficient animals results in reversal of hyperglycaemia and increases insulin production and pancreatic β-cell proliferation, supporting the view that bone tissue is involved in glucose metabolism. This evidence is further supported by human studies that show associations between insulin resistance and osteocalcin levels in plasma. The undercarboxylated form of osteocalcin has been shown in human studies involving postmenopausal women, to be associated with lower body weight, lower body fat mass and higher plasma adiponectin concentrations, supporting a role for skeletal regulation of energy metabolism in humans.
Researchers1 have investigated the association between the circulating forms of osteocalcin and insulin secretion in 78 elderly men who were considered at risk of cardiovascular disease. Following adjusted multivariate linear regression analysis, the authors reported that increases in plasma osteocalcin in the subjects was significantly associated with increases in the homeostasis model assessment of β-cell function (HOMA-BCF). In addition, the plasma concentration of undercarboxylated osteocalcin was associated with improvements in the homeostasis model assessment for insulin resistance (HOMA-IR). Baseline osteocalcin concentrations were associated with higher fasting insulin concentrations and HOMA-BCF following adjustment for confounding variables, in those not taking ant-diabetic drugs. These results suggest that plasma osteocalcin and undercarboxylated osteocalcin are associated with lower insulin secretions and increased insulin sensitivity in elderly men, and further support the contention that skeletal tissue is involved in glucose metabolism.
Osteocalcin undergoes post-translational carboxylation via the activity of a vitamin K dependent carboxylase enzyme. Traditionally, osteocalcin in the plasma was considered a marker of bone formation because osteocalcin is produced in osteoblasts. Therefore the link between dietary calcium and osteocalcin has been reported, although the exact relationship between the two is not straightforward and is still controversial despite a voluminous body of research. Both the carboxylated post-translational and undercarboxylated pre-translational forms of osteocalcin are found in plasma. The role of osteocalcin in glucose metabolism opens the possibility that dietary factors other than vitamin K and calcium might affects the synthesis and regulation of osteocalcin. However, no such nutrients have been identified. The research associating calcium with lower body weight is interesting because it brings together bone and glucose metabolism. However, more research will be needed to fully understand the role of osteocalcin in glucose metabolism.
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