Scientists from Children's Hospital of Pittsburgh have identified a molecular link between insulin resistance and inflammation.
According to senior author Dr H. Henry Dong, assistant professor, Department of Pediatrics, University of Pittsburgh School of Medicine, signs of low-grade systemic inflammation are common 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.
Advertisement"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 said.
"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," the expert added.
During the study, researchers 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.
They 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 signalling. 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," said Dong.
"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," he added.
The study appears in online version of Diabetes, one of the journals of the American Diabetes Association.