Role of Osteocalcin in Glucose Metabolism

What is it about?

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.

Featured Image

Photo by Matt C on Unsplash

Photo by Matt C on Unsplash

Why is it important?

The silent contributions of bone in endocrine regulation of glucose and fat metabolism and energy homeostasis begin to unfold. The bone as an endocrine organ offers incentive in the form of unOCN and its other endocrine secretions (FGF23, LCN2) in lieu of energy utilized during bone remodeling. The unOCN then signals back in a feed forward loop to regulate glucose homeostasis. Until now, only one known putative receptor i.e., GPRC6A is identified for unOCN. But signaling through GPRC6A does not fully explain all the events of a signaling cascade occurring in β cells, upon unOCN induction. Remarkably, the possibility of the existence of crosstalk between different signaling pathways cannot be ruled out, noticeably because insulin signals through receptor tyrosine kinases, whereas unOCN signal transmission involves a G protein coupled receptor in common target tissues to achieve similar metabolic phenotypes e.g., normoglycaemia.

Perspectives