According to a study, the DNA isolated from the muscles of people with diabetes have a different structure and expression than they do in healthy people.

Type 2 diabetes is characterized by a lower sensitivity to insulin in muscles and organs, and a reduced ability to consume energy in the form of glucose.

The epigenetic marks identified in this study are specifically found on a gene that controls the amount of fuel, in the form of glucose or lipids, that cells burn. Those marks also show up in the skeletal muscle of people with pre diabetes, suggesting that the DNA modification might be an early event in the development of diabetes.

The researchers show that genes in the muscle cells of patients with diabetes are chemically modified through what is known as DNA methylation. They found that in muscles cells taken from patients with early-onset diabetes, a gene designated as PGC-1α was modified and had reduced expression. PGC-1α controls other genes that regulate the metabolism of glucose by the cell.

DNA methylation is a form of epigenetic regulation, a process involving chemical modifications that are imposed externally on genes and that alter their activity without any change to the underlying DNA sequence.

DNA methylation of the gene also takes place in isolated muscle fiber cells when they are exposed to an inflammatory factor or to free fatty acids. "These changes take place when you expose muscle to systemic factors that mimic the diabetic condition," said study leader Juleen Zierath. They suggest a way that environmental factors, what we eat or how active we are, may perhaps influence our genes, for better or for worse.

"It's a much more dynamic process than we thought," Zierath said. "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."

Evidence that dietary factors might influence epigenetic gene control in diabetes had been suggested previously by a generational study in humans, which showed that the nutritional status of the grandparent is closely linked to an increased risk of diabetes associated mortality in their grandkids. In mice, researchers have demonstrated the cross generational effects of nutrition on DNA methylation status directly.

Whether epigenetic modifications could have more immediate effects in other tissues of the body wasn't clear before now. The researchers say they don't yet know whether these epigenetic changes are reversible, but they do have evidence that they might be prevented.

In a broader sense, the discovery shows that we are not "victims of our genes," she adds. "It's exciting because there may be ways for us to lower disease risk if physical activity or other lifestyle factors can positively influence our epigenome and improve metabolism."

"This type of epigenetic modification might be the link that explains how environmental factors have a long-term influence on the development of type 2 diabetes," says Zierath, "It remains to be seen whether the DNA methylation of this gene can be affected by, say, dietary factors."
References:
1. Romain Barrès, Megan E. Osler, Jie Yan, Anna Rune, Tomas Fritz, Kenneth Caidahl, Anna Krook, Juleen R. Zierath. Non-CpG Methylation of the PGC-1α Promoter through DNMT3B Controls Mitochondrial Density. Cell Metabolism, Volume 10, Issue 3, 189-198.