Friday, August 10, 2007

Bones May Be A Factor Contributing To Type 2 Diabetes (in Mice, Anyway)

I generally do not report much on issues pertaining to type 2 diabetes, in part, because of the the fact that so much of that news is what I would consider to garbage. Because I am not personally impacted by type 2 diabetes, many of these developments have little personal relevance to me. However, there are occasional exceptions that impact all people with diabetes. Sometimes discoveries have implications for a much wider audience, including society as a whole as well as a factor contributing to beta cell proliferation. I should forewarn and caution my readers that discoveries on mice may be irrelevant to humans.

Researchers at Columbia University Medical Center have recently identified a surprising yet critically important novel function of the skeleton. They've shown for the first time that in addition to being calcified, inert structures, the skeleton is also an endocrine organ that helps control blood glucose metabolism and weight and may therefore be a contributor to the development of type 2 diabetes.

Perhaps we shouldn't be too surprised. After all, we know that bone marrow found within large bones is responsible for producing new blood cells, and we also know that disorders in this function is responsible for leukemia. However, the Columbia researchers found that a protein made only by bone-forming cells (osteoblasts) called osteocalcin was not merely a structural protein as widely thought. Osteocalcin is also a hormone with totally unanticipated yet crucial functions. The research, which was published in the August 10, 2007 issue of the scientific journal Cell, demonstrates that bone cells release a hormone called osteocalcin, which controls the regulation of blood glucose and fat deposition through synergistic mechanisms that were previously not recognized.

As it turns out, osteocalcin directs the pancreas' beta cells, which produce the body's supply of insulin, to produce more insulin. At the same time, osteocalcin directs fat cells to release another hormone called adiponectin, which thereby improves insulin sensitivity. It has previously been shown that people with type 2 diabetes have have low osteocalcin levels, suggesting that altering the activity of this molecule could potentially be an effective therapy. That hypothesis is supported by the Columbia research, which showed that mice with high levels of osteocalcin activity were prevented from gaining weight or becoming insulin-resistant even when they ate a high fat diet. Analysis of mice lacking the osteocalcin protein showed that they developed type 2 diabetes, increased fat mass, a decrease in insulin and adiponectin expression, and decreased beta-cell proliferation.

The authors showed, in mice at least, that an increase in osteocalcin activity prevents the development of type 2 diabetes and obesity, potentially opening the door for novel therapeutic avenues (e.g. drugs) for the prevention and treatment of type 2 diabetes.

"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," said Gerard Karsenty, M.D., Ph.D., chair of the department of Genetics and Development at Columbia University Medical Center, Paul Marks Professor in the Basic Sciences, and senior author of the paper. "These results uncover an important aspect of endocrinology that was unappreciated until now."

Karsenty and his colleagues had previously shown that leptin, a hormone released by fat cells, acts upon and ultimately controls bone mass. They reasoned that bones must in turn communicate with fat, so they searched bone-forming cells for molecules that could potentially send signals back to fat cells.

This discovery showed for the first time that one hormone has a synergistic function in regulating insulin secretion and insulin sensitivity, and that this coordinating signal comes from the skeleton. Additionally, osteocalcin enhances the production of insulin-producing beta cells, which is considered one of the best, but presently unattainable, strategies to treat diabetes.

This research was supported by the National Institutes of Health, the American Diabetes Association, the Japan Society for the Promotion of Science, and the Pennsylvania Department of Health.

Note: This story has been adapted from a news release issued by Columbia University Medical Center. Photo: Agricultural Research Service (ARS)/U.S. Department of Agriculture.

1 comment:

Anne Findlay said...

nice skeleton there...

I also saw this article yesterday and was surprised to read about it. I wonder how it all ties in to increased insulin sensitivity to exercise. I don't think it's well-known why exactly exercise would improve insulin sensitivity but maybe this is a clue. Could it be that the forces exerted on bones somehow increase the concentration of osteocalcin via the adiponectin route? maybe that's too simple!

very interesting discovery...