A team of scientists has 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.
Johns Hopkins scientists' discovery sheds light on a long-hidden connection and, they say, could eventually lead to new ways of preventing and treating diabetes.
Gerald Hart said that sugar itself isn't toxic, so it's been a mystery why high blood sugar can have such a profound effect on the body, adding that the answer seems to be that high blood sugar disrupts the activity of a molecule that is involved in numerous processes within the cell. Partha 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-GlcNAcase, were down.
Banerjee noted that they expected the enzyme levels to be different in diabetes, but they didn't expect the large difference they saw. 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. The study appears online in Proceedings of the National Academy of Sciences.
