Type 2 diabetes is classified as a metabolic disorder, but a growing number of researchers are beginning to think of it also as a disease of the innate immune system. Inflammation, a key component of the early immune response, is chronically elevated in people with type 2 diabetes. While the pro-inflammatory pathways of type 2 diabetes have received much attention, the anti-inflammatory side of the equation is less well known.
The new study focused on a number of cytokines, protein signals that bind to specific receptors on cells and set off a cascade of biochemical reactions within the cell. Interleukins, interferons, tumor necrosis factors and some growth factors are among the cytokines that direct many aspects of the immune response. Cytokines are secreted by many types of cells, including the immune cells known as macrophages.In earlier studies, the researchers had shown that macrophages in diabetic and obese (diabese) mice secrete more pro-inflammatory and less anti-inflammatory cytokines than those of nondiabese mice. The team, led by pathology professor and department head Gregory Freund, also had demonstrated that human monocytes cultured under type 2 diabetic conditions had impaired interleukin-4 signaling. Interleukin
4 (IL-4) is an important player in the immune response in that it steers macrophages toward the production of other anti-inflammatory cytokines. It also inhibits secretion of the pro-inflammatory cytokines.
When IL-4 binds to its receptor on a target cell, it sets off one of two cascades of intracellular events.
The first of these signal transduction pathways, the Jak-STAT pathway, is well studied and well understood. The second, called the insulin receptor substrate 2 / phosphatidylinositol-3 kinase (IRS-2/PI3K) pathway, was more of a mystery, and of greater interest to Freund and his colleagues.
What drew them to this pathway was its potential role in the anti-inflammatory response, and its similarity to the cascade initiated when cells respond to insulin.
"One of the actions of diabetes is to create intracellular insulin resistance," Freund said. "Some of the cytokines that work on cells share the same pathways as the insulin receptor." Since diabetes causes insulin resistance, Freund said, "shouldn't there be a resistance to cytokines, too? And that is what we found."
The research team showed, for the first time, that the IRS-2 signaling arm of the interleukin-4 pathway directed the up-regulation of a key anti-inflammatory molecule in primary macrophages, and that this pathway was disrupted in type 2 diabetic conditions. They also showed that the loss of IL-4 function in diabese mice caused chronic over-expression of an important suppressor of cytokine signaling (SOCS) protein. This SOCS-3 protein aborts the cascade of events that normally leads to insulin uptake and/or cytokine signaling in a balanced inflammatory response.
This study supports earlier findings that inflammation is a key part of the pathology of diabetes, Freund said. Pro-inflammatory cytokines are elevated in type 2 diabetes, but the anti-inflammatory mechanisms are also impaired, leading to a multitude of major and minor health issues in the diabese.
"They get a cold. They get injured. Something happens. And it's worse in those people with obesity or diabetes and lasts longer than it does in others," Freund said. "Why? The imbalance may be the elevation in pro-inflammation. But it probably also includes a loss of anti-inflammatory function."
This research was supported by grants from the National Institutes of Health, American Heart Association, and the U. of I. Agricultural Experiment Station.
Diana Yates | University of Illinois
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences