High Blood Glucose Levels in Diabetes Disrupts Mitochondria

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(Last Updated On: April 2, 2020)
Normal mitochondria and mitochondria with high blood glucose level in diabetes
Microscopic image showing mitochondria in normal condition and in high blood glucose levels condition (diabetes). Image: Partha Banerjee/Johns Hopkins Medicine

High Blood Glucose levels in Diabetes affect the O-GlcNAcylation of mitochondrial proteins and lead to the disruption of the mitochondria, the powerhouse of the cell. A team of scientists from Johns Hopkins University, School of Medicine, discovered a “cause-and-effect” link between the dysregulation of O-GlcNAcylation in mitochondria and the chronic high blood glucose (sugar) level.


This finding was published in the Proceedings of the National Academy of Sciences of the United States of America, on April 27, 2015. This provides information on a long unresolved connection between diabetes and high blood glucose level and could eventually lead to a new way to prevent and treat diabetes.

Glucose itself is not toxic but is an essential biomolecule to life. So, why can high blood glucose have such a profound effect on the body? Dr. Gerald Hard, the director of the Johns Hopkins University, school of medicine said that the high blood glucose levels may disrupt the activity of the biomolecules that are involved in a variety of biological and cellular processes.

According to the previous study, high blood glucose levels of untreated diabetic person alter the mitochondrial activity. A postdoctoral fellow Dr. Parthu Banerjce performed a comparison of mitochondrial enzymes from the hearts of rats suffering from diabetes with that of the mitochondrial enzyme from the heart of the healthy rats. He closely analyzed the levels of two enzymes involved in the addition and removal of O-GlcNAc to the protein (O-GlcNAcylation).

Action of O-GlcNAc transferase during high blood glucose levels
O-GlcNAc Transferase catalyzes the transfer of N-Acetyl Glucosamine to the Protein at hydroxyl oxygen atom of Serine residue. Image: Common Wikimedia

He found that O-GlcNAc Transferase catalyzing the addition of O-GlcNAc to the protein was higher in level in the diabetic rat while the level of another enzyme O-GlcNAc Hydrolase (O-GlcNAcase) that catalyzes the removal of O-GlcNAc from the protein was lower.

He and his colleagues said that they also found the location of one of the enzymes in the mitochondria was different in the diabetic mice as compared to that of the healthy mice. To produce energy, an intricate interplay between enzyme complexes embedded in the membrane of the mitochondria is required and one of these enzyme complexes embedded in the mitochondrial membrane is O-GlcNAc Transferase, but in the case of the diabetic mice, most of the O-GlcNAc Transferase enzyme is present inside of the Mitochondria not in the membrane.

These changes in the O-GlcNAc -related enzyme activities make mitochondrial energy production less efficient that causes the mitochondria to produce more heat and damaging molecules as a byproduct. To scavenge these damaging molecules (free radicals and Reactive Oxygen Species), the liver produces antioxidants like glutathione. These processes involve more glucose production, causing an increase in the blood glucose level.

These findings reveal that any medication that can normalize the activity of these two enzymes related to O-GlcNAc could be used as an effective way to prevent or treat diabetes.

Reference: Proceedings of the National Academy of Sciences of the United States of American (Diabetes-associated dysregulation of O-GlcNAcylation in rat cardiac mitochondria).
Article DOI: 10.1073/pnas.1424017112

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