An international team of scientists has discovered that bone plays an important role in controlling sugar metabolism, energy balance and weight, suggesting the skeleton is actually a member of the endocrine system. The finding adds a surprising and unexpected footnote to our understanding of metabolism and may lead to new ways to prevent and treat type 2 diabetes.

The study which is published in the August 10th issue of the journal Cell, was carried out on laboratory mice by researchers in New York, Chicago and Hershey, Pennsylvania in the US, Seoul in Korea, Lyon in France, Cambridge in the UK, and Montreal in Canada.

Most people imagine the skeleton to be an inert calcified structure that just stops us collapsing inside our skin.

Senior author of the paper, Dr Gerard Karsenty, chair of the department of Genetics and Development at Columbia University Medical Center, and Paul Marks Professor in the Basic Sciences, explained:

“The discovery that our bones are responsible for regulating blood sugar in ways that were not known before completely changes our understanding of the function of the skeleton and uncovers a crucial aspect of energy metabolism.”

“These results uncover an important aspect of endocrinology that was unappreciated until now,” he added.

Karsenty and colleagues had a hunch that bone might be involved in metabolism because leptin, a hormone released by fat cells, is also involved in the control of bone formation. So they decided to look for other molecules that might be communicating between bone forming cells and the endocrine system.

Using laboratory mice they discovered previously unknown metabolic processes where a hormone called osteocalcin that is known to regulate mineralization and is released in bone forming cells known as osteoblasts, also regulates glucose (blood sugar) and the deposition of fat.

The scientists showed that an increase in osteocalcin effectively prevents the development of type 2 diabetes and obesity in the laboratory mice.

This is an exciting finding because it suggests increasing levels of osteocalcin in patients with type 2 diabetes could be a promising treatment route, especially since such patients tend to have low levels of the hormone.

Osteocalcin was thought only to be involved in bone development, but it seems it has a second crucial role in the endocrine system: it increases the secretion of insulin and it increases sensitivity to insulin. It also boosts production of pancreatic beta cells that make insulin (a much sought but currently unattainable path in new treatment research for type 2 diabetes) and reduces fat deposits by interacting with fat cells.

When Karsenty and colleagues analysed mice that did not have osteocalcin, they found they had type 2 diabetes, increase fat deposits, a decrease in insulin, a decrease in adiponectin expression (a protein that regulates fat deposits), and a much lower count of beta cells in the pancreas.

It came as a complete surprise to the research team, to discover that endocrine processes in the pancreas and fat cells were also being controlled by signals from the skeleton.

Karsenty and colleagues concluded that:

“By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism.”

Their next step is to look at the link between osteocalcin, blood sugar, type 2 diabetes and obesity in humans.

“Endocrine Regulation of Energy Metabolism by the Skeleton.”
Na Kyung Lee, Hideaki Sowa, Eiichi Hinoi, Mathieu Ferron, Jong Deok Ahn, Cyrille Confavreux, Romain Dacquin, Patrick J. Mee, Marc D. McKee, Dae Young Jung, Zhiyou Zhang, Jason K. Kim, Franck Mauvais-Jarvis, Patricia Ducy, and Gerard Karsenty.
Cell, Vol 130, Issue 3, 456-469, 10 August 2007

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Written by: Catharine Paddock