Glycation of Nuclear Pyruvate Dehydrogenase Restricts Acetyl-CoA and Drives Epigenetic Memory in Type 2 Diabetes

In Type 2 Diabetes (T2D) high sugar levels create harmful chemicals called dicarbonyls. These chemicals attach to proteins in a process called glycation and can alter how those proteins work. We study a protein called the pyruvate dehydrogenase complex or PDC. This protein moves into the nucleus of the cell and helps make acetyl CoA, a small molecule that keeps DNA open and active. We propose that when glycation affects PDC the cell makes less acetyl CoA, the DNA becomes tighter and important genes that regulate blood sugar level slow down. This tighter DNA state can stay in place even after blood sugar improves. This creates an epigenetic memory which means the cell continues to act as if it is still under stress. By understanding how glycation changes PDC and creates this long lasting effect we hope to find new ways to prevent or reverse these changes in diabetes.

Faculty Supervisor:

Seyed Amirhossein Tabatabaei Dakhili;John Ussher

Student:

Partner:

Toho University

Discipline:

Life Sciences

Sector:

Health and Related Sciences & Technology

University:

University of Alberta

Program: