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Finding of key blood sugar controller could yield new diabetes drugs

BOSTONDana-Farber Cancer Institute researchers have discovered the long-sought molecular "switch" that regulates the livers production of glucose, the sugar that fuels the brain but which builds up dangerously in the bloodstream of diabetics because this switch doesnt turn off. The researchers say it may be possible to design new drug treatments for diabetes as a result of the work.

The finding describes for the first time the exact on-off mechanism that in normal people helps the body maintain a precise level of glucose in the blood. Its a delicate and crucial balance. The brain depends on a constant supply of glucose no matter whether the person is eating a big meal or fasting. But the healthy range of blood sugar is narrow, and when theres too much, as in diabetes, the person is prone to serious complications.

J. Cliff Yoon, MD, MPH, and others in the laboratory of Bruce Spiegelman, Ph.D., in the department of cancer biology at DFCI are publishing the finding in the Sept. 13 issue of Nature. Other authors include Christopher B. Newgard, Ph.D., at the University of Texas Southwest Medical Center, and C. Ronald Kahn, MD, president and director of the Joslin Diabetes Center and professor of medicine at Harvard Medical School.

The biochemical switch is a previously known protein called PGC-1 that is active in liver cells, where glucose is made and secreted into the blood stream for transport to the bodys organs. The manufacture of glucose, known as gluconeogenesis, normally is turned on when a person who has fasted for a number of hours, resulting in less glucose in the blood. Insulin, the hormone that helps the body use glucose properly, signals the liver to turn off glucogenesis when there is danger of high blood sugar. But insulin is lacking or ineffective in the roughly 16 million people in the United States who have diabetes.

Now that theyve shown PGC-1 is the key regulator that insulin and other hormones act
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Contact: Janet Haley Dubow
janet_haley@dfci.harvard.edu
617-632-4090
Dana-Farber Cancer Institute
12-Sep-2001


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