Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Misfiring proteins tied to inflammation and sick feeling of type 2 diabetics

28.07.2004


After a series of studies in the laboratory of Dr. Gregory Freund, a clearer picture is emerging: A disruption of signaling proteins in the immune system may be responsible for the inflammation that makes someone with type 2 diabetes feel sick and increases the risk of serious complications.



Freund, the head of the pathology department in the University of Illinois College of Medicine at Urbana-Champaign and a professor of animal sciences in the College of Agricultural, Consumer and Environmental Sciences, is pursuing the theory that inflammation is tied to a disturbance of signal-carrying cytokines.

Type 2 diabetes – once considered an adult-onset disease – is an increasing problem alongside obesity, even among teenagers. Some 18 million Americans suffer from diabetes, with more than 90 percent being type 2, according to the Centers for Disease Control. The disease costs some $98 billion a year to treat and is the nation’s sixth leading cause of death – usually because of resulting cardiovascular and other complications.


The disease is initially characterized by high levels of insulin in the blood, a condition known as hyperinsulinemia, and insulin resistance, whereby cells refuse to let insulin inside. When that happens, the ability to regulate glucose levels is compromised. A mechanism thought to be a major player in the onset of insulin resistance, Freund said, is serine phosphorylation, triggered by hyperinsulinemia, of the insulin receptor substrates.

This phosphorylation, Freund said, “impacts other signaling cascades in cells, controlled by cytokines, especially ones like interleukin 4, an anti-inflammatory protein.”

A connection to the cytokine IL-4 was documented by Freund and colleagues in a study published July 2 in the Journal of Biological Chemistry.

They found that IL-4 signaling was impaired when they tested macrophages (a type of white blood cells) removed from type 2 diabetic mice. The research – funded by National Institutes of Health, American Heart Association, American Diabetes Assocation and University of Illinois Agricultural Experiment Station – followed similar findings, presented two years ago in the same journal, based on experiments in cell lines.

“In our first paper, we treated cells with insulin in a test tube,” Freund said. “In our new paper, we took the macrophages from diabetic animals and looked at the signaling abilities of the insulin receptor substrate 2, and, lo and behold, we indeed saw reduced signaling function.”

Freund’s co-authors on the new paper were Matthew E. Hartman, Jason C. O’Connor and Jonathan P. Godbout, all of animal sciences; Kyle D. Minor, a first-year medical student; and undergraduate biology-honors student Valerie R. Mazzocco.

New work in Freund’s lab shows that cytokine-dependent fever and reduced social exploration is found in type 2 diabetes mice. The neuroimmune response leading to the sickness behavior, Freund said, was linked to hypersensitivity to lipopolysaccharide and potentially to cytokine resistance.

Now Freund is asking what this signaling breakdown in the insulin receptor substrate does in patients. “Such knowledge would be applicable to many other diseases that involve inflammation and subsequent illness behavior,” he said.

The growing list of findings has led to a five-year $1.56 million grant, which was awarded to Freund in March by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases. Co-investigators are Robert Dantzer, a professor of animal sciences, and Jeffrey A. Woods, a professor of kinesiology.

There are three goals of the newly funded research, Freund said:

Determine the physiological relevance of the brain-immune interactions that occur in type 2 diabetes;

Identify mechanisms that cause the diabetic pro-inflammatory state to inappropriately augment lipopolysaccharide-induced fever and sickness behavior;

Determine if a potential new drug combination could improve neuroimmune function in diabetic mice.

That potential therapy is based on yet another recent discovery in Freund’s lab. Vanadyl sulfate, which now is used to reduce blood sugar content, improves insulin signaling and insulin-dependent glucose uptake in skeletal muscle in mice and speeds recovery from lipopolysaccharide-induced sickness behavior.

Freund theorizes that combining vanadyl sulfate with rapamycin, a drug used to lower the risk of rejection of transplanted kidneys, might reduce diabetes-associated inflammation and stabilize brain-immune system interactions.

Jim Barlow | University of Illinois
Further information:
http://www.uiuc.edu

More articles from Health and Medicine:

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>