Gene that regulates blood sugar levels identified

Washington, November 28 : American researchers at Baylor College of Medicine have identified a master gene that plays a key role in regulating blood sugar levels through experiments on mice.

Dr. Bert W. O'Malley, senior author of the study appearing in the journal Science, said that fasting for a day can cause the blood sugar levels of mice lacking steroid receptor-2 (SRC-2)-a master regulator gene called a coactivator-to plummet, and that the animals can die if they go another day without food.

The finding is surprising because mice normally live as long as seven days without food.

Dr. O'Malley's and colleagues have also found that the lack of SRC-2 prevents an important enzyme from converting sugar stored in the liver into a form that can go into the bloodstream.

According to the researchers, this finding has implications for a genetic disease called Von Gierke's disease and potentially adult-onset diabetes.

In their study report, the researchers have revealed that the symptoms they observed in the animal subjects resembled those of children born with Von Gierke's disease, a disorder that can create serious problems unless it is recognized early.

Parents of such children need to wake them every few hours and feed them because they may suffer seizures, lose consciousness or and die if their blood glucose levels drop below a certain level.

Dr. O'Malley, who worked in collaboration with researchers from Duke University Medical Center in Durham, N.C., says that SRC-2 works with an orphan nuclear receptor ROR alpha to affect the activity of the sugar-converting enzyme, glucose-6-phosphatase in the liver.

The researcher adds that the phosphorylated glucose cannot leave the liver until the enzyme removes the phosphate molecule, and that SRC-2 is critical to that removal process.

If the sugar cannot leave the liver, it remains there in the form of glycogen the build-up of which can cause the liver to fail.

"It's one of the few examples of a metabolic genetic disease that can be created by a deficiency in a coactivator," O'Malley said.

The researcher believes that potentially too much SRC-2 could raise the levels of glucose in the blood, which would call for increased production of insulin.

The pancreas often fails after being forced to produce high levels of insulin continuously, thereby resulting in adult-onset diabetes.

O'Malley and his colleagues plan to start studying the activity in humans in the near future, hoping that they can find ways to target the activity of SRC-2 with a drug.

ANI