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Pitt study finds molecular link between insulin resistance and inflammation
Date:8/26/2009

PITTSBURGH, Aug. 26 An exploration of the molecular links between insulin resistance and inflammation may have revealed a novel target for diabetes treatment, say scientists at the John G. Rangos Sr. Research Center, Children's Hospital of Pittsburgh of UPMC. Their findings were published earlier this month in the online version of Diabetes, one of the journals of the American Diabetes Association.

Signs of low-grade systemic inflammation are not uncommon among people who have the pre-diabetic condition known as metabolic syndrome, as well as in animal models of obesity and type 2, or insulin-resistant, diabetes, said senior author H. Henry Dong, Ph.D., assistant professor, Department of Pediatrics, University of Pittsburgh School of Medicine.

"But it's not yet clear if there is a cause-and-effect relationship between chronic exposure to low-grade inflammation and the onset of insulin resistance," he explained. "Other studies have shown that in patients who have inflammation and diabetes, insulin-sensitizing drugs seem to reduce inflammation while anti-inflammatory therapies improve sensitivity to insulin."

Dr. Dong's team examined the role played by a protein called Forkhead Box 01 (Fox01), which his previous research showed contributes to elevations in triglycerides in an animal model of obesity and diabetes.

In the current paper, the researchers found in cultured cells and mouse experiments that Fox01 stimulates inflammatory white blood cells called macrophages, which migrate to the liver and adipose, or fat, tissue in insulin-resistant states, to increase production of a cytokine called interleukin-1 beta (IL-1B). The cytokine in turn interferes with insulin signaling. Insulin typically inhibits Fox01, setting up a feedback loop in healthy tissues that helps regulate insulin levels.

"The findings suggest that when there is a lack of insulin or when cells such as macrophages are resistant to its presenc
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Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-647-3555
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

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