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!
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).
The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
16.08.2017 | Physics and Astronomy
16.08.2017 | Materials Sciences
16.08.2017 | Interdisciplinary Research