A plant extract used in traditional Chinese medicine to treat type 2 diabetes could form the basis for new treatments for the disease, scientists now report.
In some cases of type 2 diabetes, a person's pancreas doesn't produce enough insulin, a hormone that prompts cells to take in blood sugar. Studies have indicated that a substance called uncoupling protein 2 (UCP2), which is also secreted by pancreatic cells, reduces how much insulin is produced.
Lab animals that have the symptoms of type 2 diabetes often have high concentrations of UCP2, says diabetes researcher Bradford Lowell of Beth Israel Deaconess Medical Center in Boston. Animals engineered to lack the protein typically resist becoming diabetic even when they have risk factors such as obesity.
These findings suggest that inhibiting UCP2 might alleviate type 2 diabetes, says Lowell. However, no drug is known to block the protein's action.
In a search for UCP2-inhibiting compounds, Lowell's colleague Chen-Yu Zhang tested an extract made from the fruits of Gardenia jasminoides. Chinese-medicine practitioners have used pods from this shrub, also known as the cape jasmine, for thousands of years to treat type 2 diabetes.
Zhang, who now works at Nanjing University in China, Lowell, and their colleagues found that the extract stimulated pancreas cells taken from normal mice to secrete insulin. However, cells from mice engineered to lack UCP2 didn't respond. These results suggested that the extract contained the UCP2 inhibitor that the researchers were seeking.
To isolate the target substance, the researchers teamed with chemists who separated the extract into its individual components. Tests showed that one of them, a small molecule called genipin, was solely responsible for the UCP2 inhibition.
Lowell notes that scientists have studied genipin because it causes proteins to stick to each other, a factor that could cause problems in a drug. Therefore, his team fashioned a genipin derivative that lacked this protein-linking activity.
When Lowell and his colleagues tested genipin and the derivative on pancreatic cells isolated from mice with a version of type 2 diabetes, both compounds caused the cells to release more insulin.
Lowell's team reports in the June Cell Metabolism that genipin could be "a starting point" for developing UCP2-inhibiting drugs, though such compounds would require years of research before hitting the market. "This approach needs much further work to find out how good it really is," Lowell says.
Diabetes researcher Michael Wheeler of the University of Toronto agrees that "more rigorous testing" needs to be done. However, he notes that a drug based on the plant extract "sounds promising."
"Obviously, medicines in all sorts of cultures come from natural products. Some of those natural products hold a lot of truth," Wheeler says.
Bradford B. Lowell
Department of Medicine
Division of Endocrinology
Beth Israel Deaconess Medical Center and Harvard Medical School
99 Brookline Avenue
Boston, MA 02215
Department of Physiology
University of Toronto
Medical Sciences Building, Room 3352
Toronto, ON M5S 1A8
State Key Laboratory of Pharmaceutial Biotechnology
School of Life Sciences
22 Hankou Road
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