Endocrine Role of Osteocalcin in Homeostatic Regulation of Glucose Metabolism

Abstract

Osteocalcin, a well-known bone formation marker, is secreted from osteoblasts and exists in fully carboxylated, partially carboxylated, and completely uncarboxylated forms. The endocrine involvement of uncarboxylated osteocalcin in glucose homeostasis has recently been confirmed. It has been demonstrated that double recessive osteocalcin mutant mice are hyperglycemic, hypoinsulinemic, and have reduced β cell numbers and insulin resistance. In contrast, leptin (an adipocyte-derived hormone) indirectly regulates the secretion of insulin in part through inhibition of osteocalcin conversion to uncarboxylated form via β2 adrenergic receptor signaling in osteoblasts. Because uncarboxylated osteocalcin is a secretagogue of insulin, which in turn positively regulates the bone formation, osteocalcin lies at the centre of the complex mechanism of glucose homeostasis and bone remodeling network.

Keywords: β2 adrenergic receptor, Bone Gla Protein, Bone remodeling, GPRC6A, Glucose homeostasis, Hyperglycaemic, Insulin, Receptor tyrosine kinase, Leptin, Sympathetic tone, Uncarboxylated osteocalcin.