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Protein holds promise as new diabetes drug target

Scientists at the pharmaceutical company Hoffman-La Roche have discovered a chemical compound that activates the glucokinase enzyme and that could lead to a new medication for type 2 diabetes. Their work, reported in the July 18 issue of Science, builds on basic science performed at Vanderbilt University Medical Center that started 18 years ago.

When Dr. Mark A. Magnuson arrived at Vanderbilt in 1985 as a postdoctoral fellow, he took on a challenging project cloning the gene for the enzyme glucokinase. At the time, it was known that glucokinase was important for the metabolism of glucose, the sugar that climbs dangerously high in the blood of patients with diabetes. The cloning project was a success, and now, with the work by Hoffman-La Roche, glucokinase is taking center stage as a new drug target for type 2 diabetes.

"There have not been that many new drugs for the treatment of diabetes ever discovered, and this one is unique in its mechanism of action," said Magnuson, assistant vice chancellor for Research and a co-author of the report. "By turning on glucokinase, this novel compound improves insulin secretion by the pancreas and stimulates glucose usage by the liver, both of which are abnormal in diabetes." Magnuson cautions that it's too early to tell what the real value of a glucokinase-activating drug might be. Clinical trials are still in the planning stage. "It has dramatic effects in animals, suggesting it has the potential to be a very powerful new drug," he said.

The promise of such a drug comes from its target, glucokinase. This enzyme a "glucose sensor" plays a key role in maintaining sugar balance in the body. It acts mainly in the pancreatic beta cell, where it is important for insulin secretion, and in the liver, where it participates in how glucose is used and stored. Because both insulin secretion and glucose utilization by the liver are defective in patients with diabetes, a single drug that improves both functi
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Contact: Clinton Colmenares
clinton.colmenares@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
17-Jul-2003


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