And speaking of overeating, I spent 7 months losing 28 pounds for Fatty's B7 Challenge. After my final weigh-in on August 1, I began a systematic program of overeating and gained 15 pounds in 11 days. Time for me to start eating healthy again.
--pws
from http://www.boston.com/news/globe/health_science/articles/2007/08/13/surprise_diabetes_clue_found_in_bones/
Surprise: Diabetes clue found in bones
As medicine struggles to halt the nation's diabetes epidemic, scientists have found a potential new weapon in the most unlikely place -- the skeleton.
Bone cells, they discovered, generate a hormone that helps regulate the body's metabolism. And the lack of that hormone appears to contribute to the development of diabetes.
The work, conducted in mice, has a long way to go before it could be used to help diabetics. But a previous study showed that the substance, called osteocalcin, is found in lower quantities in people with untreated type 2 diabetes, scientists said.
"One could hope and certainly we will test if it could be a treatment for type 2 diabetes," said Dr. Gerard Karsenty, senior author of the paper in Cell magazine and chairman of the department of genetics and development at Columbia University Medical Center. "What makes osteocalcin attractive is that we all have it in our bodies and we tolerate it very well."
The study, which is the first to provide evidence for a skeletal hormone, is generating excitement among diabetes researchers. But they cautioned that it is only one of a number of substances that appear to interact to control blood sugar in the body, and scientists must learn much more before osteocalcin could be considered a medicine.
"It has opened up a new area" of research, said Dr. C. Ronald Kahn, head of obesity research at the Joslin Diabetes Center, who was not involved in the work. "But it's so unexpected, it's going to take a number of studies to figure out if this applies to humans."
In type 2 diabetes, sugar can rise to dangerous levels in the blood because the body loses sensitivity to insulin and may eventually not produce enough insulin. The body needs insulin to move digested food into cells to fuel activities. About 20 million Americans have this type of diabetes, which can lead to serious complications or death if not properly treated.
Scientists have known for years that osteocalcin is produced by osteoblasts, cells that help build bone. But the Columbia researchers are the first to show that it is also an endocrine hormone -- a substance that acts through the bloodstream to affect metabolism.
In their experiments, they inactivated mouse genes that produce osteocalcin. The osteocalcin-deficient mice grew abnormally fat and developed symptoms of diabetes, even when eating a normal diet. When the researchers gave the mice osteocalcin, the rodents' blood sugar normalized. Presence of the hormone also prevented mice from gaining weight when they overate.
Karsenty said the hormone appears to work in multiple ways to counter diabetes: it increases the body's production of the pancreatic cells that make insulin, it directly increases the secretion of insulin, it enhances the body's sensitivity to insulin, and it reduces storage of fat. No drug on the market carries that kind of punch.
Kahn called that multiple effect "particularly striking" and one of the goals for any new treatment. But another specialist, Dr. Michael A. Lazar, director of the Institute for Diabetes, Obesity, and Metabolism at the University of Pennsylvania, said two of those effects seem contradictory and raise questions that need to be explained.
Typically, he said, if the body becomes more sensitive to insulin, other mechanisms would kick in to shut off insulin production and vice versa. That makes it important to understand how osteocalcin interacts with other hormones as a next step, he said.
The diabetes specialists said that mice have proved to be a useful model for learning about human metabolism because of many similarities in genes, hormones, and functions. In this case, one of the genes that affects osteocalcin function in mice is not active in humans, but Karsenty said he believes there are other genes that serve the same purpose.
Karsenty, however, acknowledged "the possibility that osteocalcin function has been lost in evolution" and is not present in people.
The next steps, he said, are to study its effect in monkeys and then in humans over the next few years.
Karsenty's group discovered the new bone-based hormone because they were looking for the symmetry that often exists in the body. They knew that most hormones are part of a feedback loop and that a fat cell hormone called leptin helps controls bone mass. So they searched for a corresponding bone hormone that controls fat, and found osteocalcin.
"As proof of the concept that the skeleton makes molecules that act as hormones, this is the first of its kind, convincing and interesting," said Lazar. "It adds another candidate to the list . . . that could help us combat diabetes. But it's premature to be giving osteocalcin injections at this time."
Alice Dembner can be reached at Dembner@globe.com. 
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