In diabetes, patients suffer a higher risk of chronic bacterial and fungal infections but until now little has been known about the mechanisms involved. Now new research led by Dr Daniel Mitchell at the University of Warwick's Warwick Medical School has found a novel relationship between high glucose and the immune system in humans.
The researchers have found that specialized receptors that recognize molecules associated with bacteria and fungi become "blind" when glucose levels rise above healthy levels. The new research may also help explain why diabetic complications can also include increased risk of viral infections such as influenza, and also inflammatory conditions such as cardiovascular disease.
The researchers looked at the similarities in chemical structure between glucose in blood and body fluids, and two other sugar called mannose and fucose. These sugars are found on the surfaces of bacteria and fungi and act as targets for receptors in our body that have evolved to detect and bind to microbial sugars to then combat the infection.
The research found that high levels of glucose outcompetes the binding of mannose and fucose to the specialized immune receptors, potentially blocking these receptors from detecting infectious bacteria and fungi. Glucose also binds in such a way that it inhibits the chemical processes that would normally then follow to combat infections. If this happens it can inhibit a range of key processes including:
It can inhibit the function of immune system receptors called C-type lectins such as MBL (Mannose-binding lectin) which are known to bind to a sugar known as mannose that is present in the structure of infectious fungal bacterial cell walls. Unlike glucose, mannose does not exist in mammals as a free sugar in the blood.
The loss of MBL function may also predispose the body to chronic inflammatory diseases, since MBL is involved in the processing and clearance of apoptotic cells (dying cells).
A number of C-type lectins tat can be affected by raised glucose levels, including MBL, but also including immune cell surface receptors DC-SIGN and DC-SIGNR, are found in key parts of our circulation and vascular system such as plasma, monocytes, platelets and endothelial cells that line blood vessels. Inhibiting the function of these key molecules in those settings could contribute to diabetic cardiovascular and renal complications.
Warwick Medical School researcher Dr Daniel Mitchell said:
"Our findings offer a new perspective on how high glucose can potentially affect immunity and thus exert a negative impact on health. It also helps to emphasize the importance of good diet on preventing or controlling diseases such as diabetes. We will build on these ideas in order to consolidate the disease model and to investigate new routes to treatment and prevention."
Notes for editors:
1. The research will be published in the journal Immunobiology and is entitled "High glucose disrupts oligosaccharide recognition function via competitive inhibition: A potential mechanism for immune dysregulation in diabetes mellitus" .
2. The full list of authors is: Dr Daniel Mitchell, Dr Harpal S. Randeva, Rebecca Ilyas, Bee K. Tan, and Daniel Zehnder of the Clinical Sciences Research Institute, University of Warwick; Hendrik Lehnert of the University of Warwick and the First Medical Department, University of Lübeck, Germany; Russell Wallis of the Department of Infection and Immunity, University of Leicester; Elizabeth J. Soilleux of the Nufﬁeld Department of Clinical Laboratory Sciences, University of Oxford; Robert B. Sim of the MRC Immunochemistry Unit, University of Oxford, UK ; and Paul Townsend of the Infection, Inﬂammation and Immunology Division, University of Southampton.
3. The pre publication version of the paper is at http://www.ncbi.nlm.nih.gov/pubmed/20674073 And the doi is :10.1016/j.imbio.2010.06.002
For further information please contact:Dr Daniel Mitchell, Clinical Science Research Institute,
Kelly Parkes-Harrison | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction