A bittersweet modification O-GlcNAc and cardiac dysfunction. Circulation Research

Data from the Framingham Study indicate that cardiacdysfunction in diabetic patients may occur withoutdocumented cardiovascular disease.1 Given the pro-found metabolic disturbance underlying diabetes, such dysfunc-tion may not be surprising. Although it would be tempting to ascribe such dysfunction to simple energetic disturbances, a study in the current issue of Circulation Research 2 suggests a specific and rather unusual suspect in cardiac biology. The inability to handle glucose properly is a hallmark of diabetes. Of course, during any dialogue of glucose handling, discussants often focus on glycolysis or glycogen storage. Although up to 99% of intracellular glucose is destined for such fates, a small fraction (1 % to 5%) of intracellular glucose is diverted to the hexosamine biosynthetic pathway which culminates in the formation of low millimolar levels of cytoplasmic uridine diphospho-N-acetylglucosamine (UDP-GlcNAc). Cells use cytoplasmic stores of UDP-GlcNAc for a variety of cell processes, but the presen