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Treatment Corrects Severe Insulin Imbalance in Animal Studies
Date:7/31/2008

--Could Become First Effective Drug for Rare Genetic Disorder in Children--

PHILADELPHIA, July 31 /PRNewswire-USNewswire/ -- Researchers have used a drug to achieve normal levels of blood sugar in animals genetically engineered to have abnormally high insulin levels. If this approach succeeds in humans, it could become an innovative medicine for children with congenital hyperinsulinism, a rare but potentially devastating genetic disease in which insulin levels become dangerously high.

"There is currently no effective medical treatment for children with the most common type of congenital hyperinsulinism," said study leader Diva D. De Leon, M.D., a pediatric endocrinologist at The Children's Hospital of Philadelphia. "This type of congenital hyperinsulinism is caused by mutations in genes that encode important potassium channels in the pancreatic beta cells." The study team, from Children's Hospital and the University of Pennsylvania School of Medicine, published their report online on July 17 in the Journal of Biological Chemistry.

In congenital hyperinsulinism (HI), genetic mutations damage the insulin-secreting beta cells in the pancreas. Insulin levels rage out of control and severely reduce blood glucose, a condition called hypoglycemia. If untreated, hypoglycemia may cause irreversible brain damage or death in children. Congenital HI occurs in an estimated one in 50,000 U.S. children, with a somewhat higher incidence among certain groups, such as Ashkenazic Jews.

For the past 20 years, the standard medical treatment for some forms of HI has been the drug diazoxide, which controls insulin secretion by opening up crucial potassium channels in beta cells. However, this drug does not work in the most common and severe forms of HI, in which mutations prevent those channels from forming.

When the abnormal beta cells are confined to a discrete portion of the pancreas, as occurs in approximately half of HI cases, precise surge
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SOURCE The Children's Hospital of Philadelphia
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