Neutrophils: White blood cells mediate insulin resistance

This is a false-colored, scanning electron micrograph of a neutrophil. Credit: UC San Diego School of Medicine

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 called macrophages. Chronic low-grade inflammation – common in adipose or fat tissue – is an important cause of systemic .

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."

Oh said neutrophils were considered to be "transient infiltrates," temporary cells (average lifespan: 5 days) that were incapable of sustaining chronic, low-grade inflammation. "Our studies now suggest neutrophils possess powerful immune modulatory effects," Oh said.

Specifically, use NE to activate a signaling pathway which triggers pathogen-eating macrophages to secrete proinflammatory molecules called cytokines. NE degrades IRS1, a key protein in the insulin signaling pathway in both liver and fat cells. Although NE has been shown to degrade this protein in lung cancer , the scientists said, the effect on insulin target tissues such as liver and adipose is striking.

The insulin-mediating role of makes them a new target for developing treatments of insulin resistance in particular and diabetes in general. "Given that NE mediates insulin resistance, one could, in theory, take an NE activity inhibitory approach to reverse or improve insulin resistance," Oh said, noting that NE inhibitors are already used for treatment of emphysema in Japan and are being tested in the United States, both for emphysema and type 1 diabetes.

Related Stories

Improving obesity-induced insulin sensitivity

Jun 01, 2012

In recent years, a growing body of evidence has linked inflammation to the development of insulin resistance. In insulin resistance, the hormone insulin is less effective in promoting glucose uptake from the bloodstream into ...

Killing 'angry' immune cells in fat could fight diabetes

Oct 07, 2008

By killing off "angry" immune cells that take up residence in obese fat and muscle tissue, researchers have shown that they can rapidly reverse insulin resistance in obese mice. The findings reported in the October Cell Me ...

Why fish oils work swimmingly against diabetes

Sep 02, 2010

Researchers at the University of California, San Diego School of Medicine have identified the molecular mechanism that makes omega-3 fatty acids so effective in reducing chronic inflammation and insulin resistance.

Recommended for you

Growing a blood vessel in a week

Oct 24, 2014

The technology for creating new tissues from stem cells has taken a giant leap forward. Three tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This is shown ...

Testing time for stem cells

Oct 24, 2014

DefiniGEN is one of the first commercial opportunities to arise from Cambridge's expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic ...

Team finds key signaling pathway in cause of preeclampsia

Oct 23, 2014

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

Oct 23, 2014

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments