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

A cellular protein from a family involved in several human diseases is crucial for the proper production and release of insulin, new research has found, suggesting that the protein might play a role in diabetes.

Mice lacking the ClC-3 channel, a passageway that allows negatively-charged chloride ions to pass through cell membranes, have only one-fifth the circulating insulin of normal mice, according to research published this month in the journal Cell Metabolism.

Researchers Deborah Nelson and Louis Philipson of the University of Chicago, senior authors on the paper, argue that the finding may explain a portion of what goes wrong in Type 2 diabetes and could help doctors find rare patients whose diabetes has a previously-undetected genetic origin.

"Chloride regulation is not really well understood, but it's at the heart of cystic fibrosis, and it is related to the regulation of how insulin gets made," said Philipson, professor of medicine and medical director of the Kovler Diabetes Center at the University of Chicago. "Now we see that it's a critical feature of how insulin gets converted from a precursor form to its most active form."

Insulin is made and released by specialized pancreas cells called Beta-cells. The cell first synthesizes a protein called pro-insulin, discovered forty years ago at the University of Chicago by Donald Steiner, which is then put inside structures called secretory granules.

Inside the secretory granule, proinsulin is chemically converted into insulin, and the granule moves to the cell surface where it can release insulin into the blood. Steiner discovered that the conversion of proinsulin to insulin must happen in an acidic environment, but how the granules make themselves acidic was unknown.

A team lead by Ludmila Deriy, a research assistant professor in Nelson's laboratory, studied genetic knockout mice missing the ClC-3 chloride channel. The blood of those mice conta
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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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