Drug Corrects Severe Insulin Imbalance in Mice

A team of researchers from Children's Hospital and the University of Pennsylvania School of Medicine has successfully tested a drug to correct levels of blood sugar in mice that had abnormally high insulin levels.

In case the results replicate in human trials, say the researchers, they may have an innovative medicine for children with congenital hyperinsulinism, a rare but potentially devastating genetic disease in which insulin levels become dangerously high.

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"There is currently no effective medical treatment for children with the most common type of congenital hyperinsulinism. This type of congenital hyperinsulinism is caused by mutations in genes that encode important potassium channels in the pancreatic beta cells," said study leader Dr. Diva D. De Leon, a paediatric endocrinologist at The Children's Hospital of Philadelphia.

A research article in the online edition of the Journal of Biological Chemistry says that, in congenital hyperinsulinism (HI), genetic mutations damage the insulin-secreting beta cells in the pancreas.

Consequently, insulin levels rage out of control and severely reduce blood glucose, a condition called hypoglycemia that may cause irreversible brain damage or death in children if not treated.

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For their study, the researchers first genetically engineered some mice to mimic the defect found in children with congenital HI, and then tested the effect of a peptide called exendin-(9-39) - which blocks the action of a specific hormone receptor in beta cells - on the subjects.

When the researchers withheld food from the mice, their blood glucose levels became low, a condition called fasting hypoglycemia.

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However, mice that had received exendin-(9-39) 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 signalling system that malfunctions in HI.

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De Leon says that the next step is a pilot study to test the effect of exendin-(9-39) in children and adults with congenital HI.

She says that her team expects to progress to a larger clinical trial, if the ongoing pilot study gives promising results.

"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," she said.

Source-ANI
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