Scientists at Johns Hopkins say they've discovered a cause-and-effect link between chronic high blood sugar and disruption of mitochondria, the powerhouses that create the metabolic energy that runs living cells. The discovery, reported online in Proceedings of the National Academy of Sciences on April 27, sheds light on a long-hidden connection and, they say, could eventually lead to new ways of preventing and treating diabetes.
"Sugar itself isn't toxic, so it's been a mystery why high blood sugar can have such a profound effect on the body," says Gerald Hart, Ph.D. , director of the Johns Hopkins University School of Medicine's Department of Biological Chemistry. "The answer seems to be that high blood sugar disrupts the activity of a molecule that is involved in numerous processes within the cell."
Previous experiments by other research groups had shown that the high blood sugar of untreated diabetes alters the activity of mitochondria, compartments that process nutrients into useable energy for cells.
To find out why, postdoctoral fellow Partha Banerjee, Ph.D., compared the enzymes in mitochondria from the hearts of rats with diabetes to those from healthy rat hearts. He looked for differences in levels of two enzymes that add and remove a molecule called O-GlcNAc to proteins. Hart's research group has for 30 years studied cells' use of O-GlcNAc to control how nutrients and energy are processed.
Banerjee found that levels of one enzyme, O-GlcNAc transferase, that adds O-GlcNAc to proteins was higher in the diabetic rat mitochondria, while levels of an enzyme that removes O-GlcNAc, O-
"We expected the enzyme levels to be different in diabetes, but we didn't expect the large difference we saw," Banerjee says. He and his colleagues say they also found that the location of one of the enzymes within the mitochondria was different in the diabetic mice.
Producing energy requires an intricate interplay between enzyme complexes embedded in mitochondrial membranes, each with a distinctive role. O-GlcNAc transferase is normally found in one of these complexes, but in the diabetic mice, much of it had migrated to the inside of the mitochondria, Banerjee says.
The net effect of the changes in O-GlcNAc-related activity, Hart says, is to make energy production in the mitochondria less efficient so that the mitochondria begin to produce more heat and damaging molecules as byproducts of the process. The liver then kicks off an antioxidant process for neutralizing so-called free radicals, which involves making more glucose, increasing blood sugar further.
Finding a medication that normalizes activity of the O-GlcNAc enzymes, he says, could be an effective way to prevent or treat diabetes.
Junfeng Ma of The Johns Hopkins University was also an author on the paper.
Hart receives a share of royalty received by the university on sales of the CTD 110.6 antibody, which are managed by The Johns Hopkins University. CTD 110.6 antibody was used in the experiments described here.
Shawna Williams | EurekAlert!
Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto
Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.
Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...
22.05.2017 | Event News
17.05.2017 | Event News
16.05.2017 | Event News
22.05.2017 | Materials Sciences
22.05.2017 | Life Sciences
22.05.2017 | Physics and Astronomy