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A false-colored, scanning electron micrograph of a neutrophil.

White Blood Cells Mediate Insulin Resistance
Neutrophils’ role is a surprise – and a potential new target for treating diabetes

Researchers at the University of California, San Diego School of Medicine say neutrophils, an abundant type of white blood cell typically tasked with attacking bacteria and other foreign invaders, also plays an unexpected role in mediating insulin resistance – the central characteristic of type 2 diabetes, which afflicts an estimated 26 million Americans.

The findings are published in the August 5, 2012 Advance Online Publication of Nature Medicine.

Neutrophils are the first immune cells to respond to tissue inflammation, and can promote chronic inflammation by summoning other white blood cells called macrophages. Chronic low-grade inflammation – common in adipose or fat tissue – is an important cause of systemic insulin resistance.

Using liver and fat cells from mice and humans and live mouse models, a team led by Jerrold M. Olefsky, MD, associate dean for scientific affairs at UC San Diego Health Sciences and professor of medicine, discovered that an enzyme secreted by neutrophils called neutrophil elastase (NE) impairs insulin signaling and boosts resistance. Conversely, deletion of NE in obese mice fed a high-fat diet improved insulin sensitivity.

“These results are largely unexpected,” said Da Young Oh, an assistant project scientist in Olefsky’s lab and study co-author. “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.”

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