Key Enzyme Implicated in Diabetes Blood Vessel Complications

Understanding how cells in the body respond to high sugar levels is critical to overcoming the complications of diabetes. The DCCT-EDIC study showed that people with diabetes maintaining intensive blood sugar control were protected against complications compared to those less actively managing their blood sugar levels. This effect persisted for over a decade, even though the less active group was later switched to receive intensive therapy and HbA1C became similar between both groups. This observation of a persistent benefit became known as metabolic memory. This new research attempted to understand metabolic memory by creating model systems where one could observe how even short spikes of high sugar levels can lead to sustained changes in cell functioning. These model systems have been used to explore the potential role of an enzyme which regulates changes to the shape of DNA in the cell and which helps to control levels of certain proteins within cells. Such changes can lead to long-term cellular changes. Using this novel model system, this research showed that this enzyme moves into the nucleus of blood vessel cells exposed to high glucose potentially leading to long-term changes in blood vessels. This work also found that this enzyme appears to target genes that can contribute to inflammation, giving a potential link to diabetes complications. The investigators have identified a distinctive signature of these modifications associated with high sugar levels. These changes were observed in both laboratory and animal models of T1D.

Reference:

Distinguishing Hyperglycemic Changes by Set7 in Vascular Endothelial Cells. Okabe J, Orlowski C, Balcerczyk A, Tikellis C, Thomas MC, Cooper ME, El-Osta A. Circ Res. 2012 Mar 8. [Epub ahead of print]

Ramifications for Individuals with Type 1 Diabetes:

Although this is early stage research, a better understanding of the long-term effects of high-glucose exposure could lead to new treatment targets, as well as help explain why different people with T1D develop diabetes complications at different rates, or not at all.

JDRF Involvement: