St. Louis, Nov. 1, 1999 -- A recent study reveals that long-term nerve damage in rats with diabetes can be reversed by treatment with an insulin-like protein. Because the damage mimics some of what's seen in people with diabetes, the results suggest that the protein could one day be used to prevent certain nerve complications of the disease.
"You may be able to prevent some diabetic nerve complications, even in people who don't control their diabetes well," says Robert E. Schmidt, M.D., Ph.D. Schmidt is a professor of pathology at Washington University School of Medicine in St. Louis. He also is lead author of an article about the study in this month's American Journal of Pathology.
As many as 60 percent of people with diabetes have some damage to the peripheral nervous system, which receives and sends messages to the hands, feet and other outlying sites in the body. Diabetic neuropathy also can occur in the sympathetic part of the autonomic nervous system, a specialized portion of the nervous system that controls involuntary reflexes. Such damage can produce complications such as irregularities in the control of blood pressure and bouts of diarrhea or constipation.
Nerve cells and their branch-like extensions called axons are vulnerable to abnormally high levels of glucose in the bloodstream that occur during diabetes. In the sympathetic nervous system, the outermost tips of axons swell into doorknob-like structures as a result. These nerve endings allow nerve cells to communicate with each other, and the swelling impedes this process. Schmidt studied the effect of an insulin-like growth factor called IGF-I on diabetic rats. His group examined the animals' sympathetic nervous tissue and determined that the neuropathy mimicked that seen in humans. "The parallels in the pathologic findings in diabetic humans and rats were so strong that we thought that similar processes were at work in rats' nerve cells as in humans with diabetes," Schmidt says.
After the rats had been diabetic for six months -- enough time for nerve damage to occur -- the researchers gave some of them daily injections of IGF-I for two months.
Compared with untreated counterparts, these rats had 80 percent fewer swollen nerve endings in the sympathetic nervous system. And the swelling tended to be less pronounced than in the untreated rats.
Schmidt is quick to note that swelling of nerve endings still occurs to a limited extent in rats treated with IGF-I. But he also has found that healthy rats develop the swellings in small numbers as they age. "A simplistic view is that diabetes might accelerate the aging of sympathetic nerve cells," he says.
He and his colleagues will evaluate the cellular changes occurring in diabetic rats to determine how the swelling occurs. They also will try to determine how IGF-I injections ameliorate the damage.
The growth factor doesn't stop diabetes in its tracks because treated animals are unable to control their blood-glucose levels. IGF-I treatment may instead compensate for the loss of a factor that keeps nerve cells healthy, or it may be a nourishing agent itself. "We have a sense of the potential relevance of the growth factor," Schmidt says. "Now we have to figure out how it works."
Researchers elsewhere are evaluating IGF-I in clinical trials on people with neurodegenerative diseases such as amyotrophic lateral sclerosis, or Lou Gehrig's disease.
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