When mice that lack steroid receptor-2 (SRC-2) a master regulator gene called a coactivator fast for a day, their blood sugar levels plummet. If they go another day without food, they will die.
The severity of the hypoglycemia (low blood sugar) was unexpected, said Dr. Bert W. O'Malley, chair of molecular and cellular biology at Baylor College of Medicine and senior author of the report on the study that appears in the current issue of the journal Science. Normal mice live as long as seven days without food.
Further examination showed 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. The finding has implications for a genetic disease called Von Gierke's disease and potentially adult-onset diabetes.
The symptoms suffered by mice resembled those of children born with Von Gierke's disease, said O'Malley. The disorder can create serious problems unless it is recognized early. Parents must wake the infants every few hours and feed them to keep their blood glucose levels up. As long as the glucose levels are high enough, the brain is nourished. If their blood glucose levels drop below a certain level, they suffer seizures, lose consciousness and can die.
Studies in O'Malley's laboratory in collaboration with researchers from Duke University Medical Center in Durham, N.C., revealed 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 liver produces 90 percent of the glucose circulating in the blood stream. Glucose stored in the liver has a phosphate molecular attached to it. This phosphorylated glucose cannot leave the liver until the enzyme removes the phosphate molecule. SRC-2 is critical to that removal process.
If the sugar cannot leave the liver, it remains there in the form of glycogen. Eventually, the buildup
|Contact: Kimberlee Norton|
Baylor College of Medicine