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
Algae: The final frontier
22.06.2017 | Carnegie Institution for Science
Flipping the switch to stop tumor development
22.06.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.
New Manufacturing Technologies for New Products
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
22.06.2017 | Physics and Astronomy
22.06.2017 | Physics and Astronomy
22.06.2017 | Materials Sciences