MCG researchers study hormone that may prevent bone being lost in space

March 22, 2001

The reality of long-term space travel is raising questions about how to deal with the impact of long-term weightlessness on the body.

Medical College of Georgia researchers say that one of the destructive results B accelerated and significant loss of bone density B may be thwarted by a hormone secreted by the gut to help the body use food as fuel.

Their research on glucose-dependent insulinotropic peptide, or GIP, is funded by the National Space Biomedical Research Institute in Houston but it also holds promise for the down-to-earth problem of bone loss that inevitably comes with age.

Dr. Carlos M. Isales, endocrinologist, and Dr. Roni J. Bollag, developmental biologist, have developed a transgenic mouse that over-expresses GIP by about four times the normal rate; that equals the increase that occurs in the body after a meal.

"We think GIP is a signal the blood sends to your bones that says,
"We think the hormone may also act with insulin to make bones stronger," Dr. Isales said. As food is eaten, GIP and insulin levels both go up, but their secretion patterns are different: GIP levels don't return to baseline as quickly.

Rather GIP hangs around longer, stimulating osteoblasts to make bone and shutting down osteoclasts that break down bone. The balance of bone loss and production is uncoupled by weightlessness and by hormonal loss that occurs with age, Dr. Isales said. "You can break down bone, but you don't form it as well," without the natural force of gravity. Bone loss and production are constants in life, with the average person reforming his skeleton three or four times. Most people reach peak bone mass at age 25 and begin losing bone by age 40. A young space traveler would never reach peak bone mass without some intervention to re-establish the lost synergy, he said; an astronaut of any age would soon develop porous, weak bones.

But the researchers believe their transgenic mouse would fare much better in space, where they hope it will eventually land. For the time being, they are using a nearly $900,000, three-year grant to study the mice on earth, simulating periods of weightlessness in the animals that over-express GIP and measuring the impact of the loss of gravity on the bones. "We think that what will happen is that those mice who over-express GIP won't lose bone," Dr. Isales said.

If they are right, GIP levels could be increased by injecting a synthetic version already commercially available for research, but the simplest way might be designing an optimal diet, he said. Carbohydrates, protein and fat all stimulate GIP production. The current thinking is that heavier people have denser bones because of increased gravity, but increased GIP production likely plays a role as well, Dr. Isales said.

They also will look at the impact of GIP on early bone development. The researchers have a mouse that expresses GIP at 10 times the natural rate.

These high levels may not only impact bone sturdiness, but also may increase bone length, he said. "We think it's involved in bone formation in the growth plate," Dr. Isales said, which means GIP supplements might also treat growth problems.

Medical College of Georgia at Augusta University

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