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Misfiring proteins tied to inflammation and sick feeling of type 2 diabetics

CHAMPAIGN, Ill. -- After a series of studies in the laboratory of Dr. Gregory Freund, a clearer picture is emerging: A disruption of signaling proteins in the immune system may be responsible for the inflammation that makes someone with type 2 diabetes feel sick and increases the risk of serious complications.

Freund, the head of the pathology department in the University of Illinois College of Medicine at Urbana-Champaign and a professor of animal sciences in the College of Agricultural, Consumer and Environmental Sciences, is pursuing the theory that inflammation is tied to a disturbance of signal-carrying cytokines.

Type 2 diabetes -- once considered an adult-onset disease -- is an increasing problem alongside obesity, even among teenagers. Some 18 million Americans suffer from diabetes, with more than 90 percent being type 2, according to the Centers for Disease Control. Diabetes costs some $98 billion a year to treat and is the nation's sixth leading cause of death -- usually because of resulting cardiovascular and other complications.

The disease is initially characterized by high levels of insulin in the blood, a condition known as hyperinsulinemia, and insulin resistance, whereby cells refuse to let insulin inside. When that happens, the ability to regulate glucose levels is compromised. A mechanism thought to be a major player in the onset of insulin resistance, Freund said, is serine phosphorylation, triggered by hyperinsulinemia, of the insulin receptor substrates.

This phosphorylation, Freund said, "impacts other signaling cascades in cells, controlled by cytokines, especially ones like interleukin 4, an anti-inflammatory protein."

A connection to the cytokine IL-4 was documented by Freund and colleagues in a study published July 2 in the Journal of Biological Chemistry. They found that IL-4 signaling was impaired when they tested macrophages (a type of white blood cells) removed from type 2 diabetic mice. <
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Contact: Jim Barlow, Life Sciences Editor
jebarlow@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
27-Jul-2004


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