How DNA changes play role in diabetes
Swedish scientists have discovered a significant difference in the structure and expression of genes that control human cell energy consumption between type 2 diabetes sufferers and healthy people. Published in the journal Cell Metabolism, the findings suggest that epigenetic changes in the body may contribute to the development of diabetes. The scientists from Karolinska Institutet in Sweden isolated the deoxyribonucleic acid (DNA) from the muscles of diabetes sufferers and discovered chemical marks that are not found in people who respond normally to rising blood sugar levels. According to the researchers, these epigenetic marks (i.e. marks arising from non-genetic external factors) are found on a gene that controls the amount of fuel, either glucose or lipids, that cells burn. They also pointed out that these marks are found in the skeletal muscle of people with prediabetes, a condition which occurs when blood sugar levels are higher than normal levels but below the diabetes mark. Failure to treat prediabetes will result in patients being diagnosed with type 2 diabetes within 10 years. The results of this study hint that the change in DNA might be an early event in the development of the disease. The scientists stated that while these modifications reprogramme the gene's activity quickly, they do not affect the underlying DNA sequence. Therefore, it is highly likely that environmental factors, such as exercise and food, have both positive and negative effects on our genes. The study shows that hypermethylation (an increase in the epigenetic methylation of cytosine and adenosine residues in DNA) of the gene called PGC-1alpha (peroxisome proliferator-activated receptor gamma [PPARgamma] coactivator-1alpha) also occurs in isolated muscle fibre cells when they are exposed to an inflammatory factor or to free fatty acids. Conversely, the changes discovered in this research occurred in cells of the body that are completely mature. 'These changes take place when you expose muscle to systemic factors that mimic the diabetic condition,' explained Professor Juleen Zierath of the Department of Molecular Medicine and Surgery at Karolinska Institutet. Professor Zierath and her colleague Romain Barrès, who is the lead author, noted that the changes to the epigenetic imprint have been seen before. According to them, the chemical modification of genes is responsible for development changes that occur as cells differentiate, which is the mechanism by which cells become specialised to perform specific functions in various tissues and organs. They are responsible for the production of keratin (a fibrous scleroprotein) in the skin, but not in blood. 'It's a much more dynamic process than we thought,' Professor Zierath pointed out. 'The genetic causes of diabetes are important, but this shows us that epigenetic changes, which take place on top of our genes, can alter our physiology in critical ways.' A past generation study in humans showed that dietary factors could probably affect gene control in diabetes. Based on the study's results, the nutritional status of grandparents is closely linked to an increased risk of diabetes-associated mortality in their grandchildren.
Countries
Sweden