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Treatment corrects severe insulin imbalance in animal studies
Date:7/31/2008

osing such lesions and performing the curative surgery on newborns.

However, when abnormal cells are distributed throughout the pancreas in so-called diffuse HI, surgeons must remove nearly all the pancreas. This relieves HI in about a quarter of cases, but leaves the majority of patients at high risk for insulin imbalance, in which blood glucose levels are too low (hypoglycemia) or too high, resulting in diabetes.

The new study makes use of a peptide (an amino acid compound) called exendin-(9-39) that blocks the action of a specific hormone receptor in beta cells. Building on their previous work using exendin-(9-39) on normal mice, De Len's study team studied the peptide's effect on a strain of mice that had been genetically engineered to mimic the defect found in children with congenital HI.

When researchers withhold food from those mice, their blood glucose levels become low, a condition called fasting hypoglycemia. Mice who had received exendin-(9-39), however, had significantly higher levels of fasting blood glucose compared to mice that were not treated with the peptide, and reached levels comparable to those in normal, healthy animals. Further studies identified the mechanisms in the hormone signaling system that malfunctions in HI.

The next step, says De Len, is a pilot study now under way to test the effect of exendin-(9-39) in children and adults with congenital HI. If results from the pilot study are promising, her study team expects to progress to a larger clinical trial. "If this peptide can be developed into a treatment for children with this common form of HI, we may have a new tool for controlling their insulin levels and managing their disease," added De Len.

The Congenital Hyperinsulinism Center at Children's Hospital has worldwide prominence in diagnosing and treating this genetic disease. Much of its work builds on pioneering research by Charles A. Stanley, M.D., in identifying the specific gene defec
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Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6050
Children's Hospital of Philadelphia
Source:Eurekalert

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