Scientists have made a surprising discovery about the role of white blood cells, known as neutrophils, and the role they play in insulin resistance that leads to type 2 diabetes. The finding means a new target for treatment for the disease from drugs that are already being tested in the United States for emphysema and type 1 diabetes.
Neutrophils' role in mediating insulin resistance unexpected
The study, published in the journal Nature Medicine, unexpectedly revealed neutrophils that are abundant in the body mediate insulin resistance.
Researchers at the University of California, San Diego School of Medicine explain the blood cells’ role is to attack bacteria and other foreign invaders.
The white blood cells also secrete and enzyme known as neutrophil elastase (NE) that impairs insulin signaling and boosts resistance. The discovery was made by a team led by Jerrold M. Olefsky, MD, associate dean for scientific affairs at UC San Diego Health Sciences and professor of medicine who studied liver and fat cells from mice and humans and live mouse models.
"These results are largely unexpected," said Da Young Oh, an assistant project scientist in Olefsky's lab and study co-author in a media release. "Although several immune cells have been established in the etiology of insulin resistance, the role of neutrophils in this process has remained unclear until now."
One of the reasons insulin resistance happens is from chronic low-grade inflammation that is common in fat tissue and why obesity is a top risk factor for type 2 diabetes.
Neutrophils are the first line of defense when inflammation occurs. The white cells recruit other cells in the body known as macrophages when an inflammatory process occurs, like the kind associated with obesity.
The result of having too much fat tissue and inflammation from neutrophils and macrophages is that when it becomes chronic it can lead a variety of inflammatory related diseases. Insulin resistance and diabetes are examples.
It was previously thought that neutrophils attacked and then left, with a life-span of about 5 days; therefore not capable of causing chronic, low-grade inflammation. "Our studies now suggest neutrophils possess powerful immune modulatory effects," Oh said.
Neutrophils signal NE to trigger the release of inflammation producing chemicals known as cytokines by macrophages. NE also breaks down an important protein in the insulin signaling pathway in the liver and fat cells known as IRS1. The researchers found out the effect of NE in liver and in fat tissue is ‘striking’.
The finding means potential new targets for treating for diabetes in addition to new ways to thwart the disease by treating insulin resistance – sometimes called pre-diabetes - before it actually develops.
Oh said NE inhibitors are already used for treatment of emphysema in Japan. In the United States they are being tested emphysema and type 1 diabetes.
He says ‘in theory’ you could also take neutrophil elastase inhibitors and reverse or improve insulin resistance. The discovery of neutrophils' role in promoting inflammation and insulin resistance means a potential new target for preventing and treating diabetes.
"Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase"
Saswata Talukdar, Da Young Oh, et al.
August 5, 2012
Image: Neutrophil white blood cells
Credit: Wikimedia commons