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A University of Texas researcher who genetically modified mice with type 1 diabetes to control their disease with leptin instead of insulin is now ready to extend his experiment to human test subjects. Dr. Roger Unger, a researcher at the UT Southwestern Medical School in Dallas, will begin the tests as soon as leptin manufacturers can assure him of a steady supply of the hormone.
While other studies have indicated that the hormone may help control blood sugar levels, Unger and his associates were the first to experiment with leptin as a monotherapy in diabetes.
In his paper, "Leptin monotherapy in insulin dependent type 1 diabetes," just published in the Proceedings of the National Academy of Sciences, Unger details how his team initially genetically modified diabetic mice to produce extra quantities of leptin. The mice were then taken off insulin and left to rely solely on leptin to control their blood sugar levels.
Unger reports that the mice thrived on the insulin-free regimen. Because genetic manipulation is not an option in human test subjects, the next step was to treat diabetic mice that had not been genetically altered with pump-delivered injections of leptin. Unger reports that those mice, too, did well despite the absence of insulin.
One reason for Unger's desire to see if leptin can be a viable alternative to insulin is concern about the side effects produced by the typically large doses of insulin that most people with type 1 diabetes have to take. Among them are large fluctuations in blood sugar levels and possible long-term ill effects on blood vessels. In his experiments with leptin, Unger found that only low doses of the hormone were needed to maintain stable blood sugar levels.
Even as he undertakes tests with human subjects, Unger agrees with other diabetes experts that there is still a long way to go before leptin could be recommended as an alternative diabetes therapy. One important question the research may help answer is why leptin mimics insulin's ability to deliver sugar to muscles and fat cells.
In comments on his paper, Dr. Barbara Kahn, a diabetes expert at Harvard Medical School and chief of endocrinology at Beth Israel Deaconess Medical Center in Boston, said that Unger's research will have to address several other crucial questions:
Whatever answers Unger's further research delivers, they probably won't help people with type 2 diabetes, who are resistant to both insulin and leptin.
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