Children's Researchers Find Molecular Links Between Insulin Resistance And Inflammation
Gumbo
Inflammation
Main Category: Diabetes
Article Date: 27 Aug 2009 - 0:00 PDT
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 presence, there are no brakes on
Fox01's stimulation of IL-1B and its further interference with insulin
signaling," Dr. Dong said. "That might explain why chronic inflammation
often is coupled with obesity and type 2 diabetes. Also, a drug that acts on
Fox01 might be able to better control blood sugar."
According to the ADA, an estimated 24 million Americans have type 2
diabetes, formerly known as adult-onset diabetes. As obesity becomes more
common, however, the prevalence is rising in children. In type 2 diabetes,
the body becomes resistant to the effect of insulin, leading to elevated
blood sugar levels.
Co- authors of the paper include lead author Dongming Su, M.D., Gina M.
Coudriet, Dae Hyun Kim, Ph.D., German Perdermo, Ph.D., Shen Qu, M.D., Sandra
Slusher, Hubert M. Tse, Ph.D., Jon Piganelli, Ph.D., and Nick Giannoukakis,
Ph.D., all of the Division of Immunogenetics, Department of Pediatrics,
Children's Hospital of Pittsburgh of UPMC and Pitt School of Medicine, and
Yi Lu, Ph.D., and Jian Zhang, M.D., Division of Hematology and Oncology,
Department of Medicine, Pitt School of Medicine.
The study was funded by the American Diabetes Association and the National
Institutes of Health.
Source
University of Pittsburgh School of Medicine
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