Published online Dec 25, 2015. doi: 10.4239/wjd.v6.i18.1345
Peer-review started: August 24, 2015
First decision: October 13, 2015
Revised: October 23, 2015
Accepted: December 1, 2015
Article in press: December 2, 2015
Published online: December 25, 2015
The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate osteocalcin expression in osteoblasts, suggesting that positive feedforward loops exist among bone, pancreas, and adipose tissue. In addition, recent studies have shown that osteocalcin enhances insulin sensitivity and the differentiation in muscle, while secreted factors from muscle, myokines, regulate bone metabolism. These findings suggest that bone metabolism and glucose metabolism are associated with each other through the action of osteocalcin. In this review, I describe the role of osteocalcin in the interaction among bone, pancreas, brain, adipose tissue, and muscle.
Core tip: Osteocalcin, especially undercarboxylated form of osteocalcin, has an endocrine function to regulate glucose metabolism. Osteocalcin directly stimulates insulin secretion in pancreas and indirectly via increasing glucagon-like peptide-1 secretion in small intestine as well as adiponectin secretion in adipose tissue, and enhances insulin sensitivity in muscle. Therefore, osteocalcin may be an important factor linking between bone and glucose homeostasis.