DNA mutations linked to diabetes

Type II diabetes is characterised by a lower sensitivity to insulin in muscles and organs, and a reduced ability to consume energy in the form of glucose. Heredity and environmental factors (e.g. exercise) are both involved in the disease pathogenesis, but scientists are still unclear as to the mechanisms behind it.

A research group at Karolinska Institutet has now shown that genes in the muscle cells of diabetics 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-1¦Á was modified and had reduced expression. PGC-1¦Á controls other genes that regulate the metabolism of glucose by the cell.

The team has also demonstrated that DNA methylation occurs rapidly, when cells from healthy people are exposed to certain factors associated with diabetes, such as raised levels of free fatty acids and cytokines. 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.

“This type of epigenetic modification might be the link that explains how environmental factors have a long-term influence on the development of type II diabetes,” says Juleen Zierath, who led the study. “It remains to be seen whether the DNA methylation of this gene can be affected by, say, dietary factors.”

Full bibliographic information
¡°Non-CpG Methylation of the PGC-1¦Á Promoter through DNMT3B Controls Mitochondrial Density¡±, Romain Barr¨¨s, Megan E. Osler, Jie Yan, Anna Rune, Tomas Fritz, Kenneth Caidahl, Anna Krook and Juleen R. Zierath, Cell Metabolism, 2 September 2009.