(SACRAMENTO, Calif.) -- UC Davis Health System researchers have identified for the first time a biological pathway that is activated when blood sugar levels are abnormally high and causes irregular heartbeats, a condition known as cardiac arrhythmia that is linked with heart failure and sudden cardiac death.
Reported online today in the journal "Nature," the discovery helps explain why diabetes is a significant independent risk factor for heart disease.
"The novel molecular understanding we have uncovered paves the way for new therapeutic strategies that protect the heart health of patients with diabetes," said Donald Bers, chair of the UC Davis Department of Pharmacology and senior author of the study.
While heart disease is common in the general population, the risk is up to four times greater for diabetics, according to the National Institutes of Health. The American Heart Association estimates that at least 65 percent of people with diabetes die from heart disease or stroke and has emphasized the need for research focused on understanding this relationship.
Through a series of experiments, Bers, his UC Davis team and their collaborators at the Johns Hopkins University School of Medicine showed that the moderate to high blood glucose levels characteristic of diabetes caused a sugar molecule (O-linked N-acetylglucosamine, or O-GlcNAc) in heart muscle cells to fuse to a specific site on a protein known as calcium/calmodulin-dependent protein kinase II, or CaMKII.
CaMKII has important roles in regulating normal calcium levels, electrical activity and pumping action of the heart, according to Bers. Its fusion with O-GlcNAc, however, led to chronic overactivation of CaMKII and pathological changes in the finely tuned calcium signaling system it controls, triggering full-blown arrhythmias in just a few minutes. The arrhythmias were prevented by inhibiting CaMKII or its union with O-GlcNAc.
|Contact: Karen Finney|
University of California - Davis Health System