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Protein critical for insulin secretion may be contributor to diabetes
Date:10/26/2009

ined lower levels of insulin and cellular measurements discovered that fewer granules were released by Beta-cells from ClC-3 knockouts and that the granules of ClC-3 knockout mice were less acidic than those from normal mice.

High-powered electron microscope images allowed researchers to observe that the granules of ClC-3 knockout mice contained higher amounts of proinsulin than granules from normal mice. Missing ClC-3 therefore appears to cause a dramatic slowdown of the conversion of proinsulin to insulin inside the granules, said Nelson, professor of neurobiology at the University of Chicago.

"Not only is release down, but what is released is not as efficacious a molecule," Nelson said. "It's pro-insulin rather insulin, if anything's released at all."

A mutation in the function of ClC-3 in humans could very well be the cause of a select few cases of juvenile diabetes, Nelson and Philipson said. However, while other ClC proteins have been linked to bone, muscle and kidney disease, no human case of diabetes has yet been linked to the function of this specific protein. Because ClC-3 knockout mice also experience epileptic seizures, a patient diagnosed with both epilepsy and diabetes could potentially have an undetected defect in their ClC-3 channel.

"If it happens that there's epilepsy and diabetes, it's not currently recognized as a syndrome," Philipson said. "We would be extremely interested in cases like that."

Finding a patient with this rare form of genetically-caused diabetes could be aided by efforts such as Lilly's Law, an Illinois legislation signed in August that created a statewide diabetes registry. The law requires that doctors report all diagnoses of children younger than 12 months to the state Department of Public Health. Scientists can then test those children to see if their disease is caused by a genetic mutation, knowledge that can improve the child's treatment.

The law is named for Lilly Jaffe
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Contact: Rob Mitchum
robert.mitchum@uchospitals.edu
773-702-6241
University of Chicago Medical Center
Source:Eurekalert

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