Public Release: 

DNA mutations linked to diabetes

Karolinska Institutet

Genes that regulate the energy consumption of cells have a different structure and expression in type II diabetics than they do in healthy people, according to a new study from the Swedish medical university Karolinska Institutet published in Cell Metabolism. The researchers believe that these 'epigenetic mutations' might have a key part to play in the development of the disease.

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-1α was modified and had reduced expression. PGC-1α 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."

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Publication: "Non-CpG Methylation of the PGC-1α Promoter through DNMT3B Controls Mitochondrial Density", Romain Barrès, Megan E. Osler, Jie Yan, Anna Rune, Tomas Fritz, Kenneth Caidahl, Anna Krook and Juleen R. Zierath, Cell Metabolism, 2 September 2009.

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For further information, please contact:

Professor Juleen Zierath
Department of Molecular Medicine and Surgery (MMK)
Tel:+46 (0)8-524 875 80, +46 (0)70-767 0746
Email: Juleen.Zierath@ki.se

KI Press Office
Tel: +46 (0)8-524 860 77
Email: pressinfo@ki.se

Karolinska Institutet is one of the leading medical universities in Europe. Through research and education, Karolinska Institutet contributes to improving human health. Each year, the Nobel Assembly at Karolinska Institutet awards the Nobel Prize in Physiology or Medicine. For more information, visit ki.se

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