Senior author Donald Bers, chair of the University of California, Davis Department of Pharmacology, said that the novel molecular understanding that they have uncovered paves the way for new therapeutic strategies that protect the heart health of patients with diabetes.
Bers, his UC Davis team and their collaborators at the Johns Hopkins University School of Medicine conducted a series of experiments to show 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.
According to Bers, CaMKII has important roles in regulating normal calcium levels, electrical activity and pumping action of the heart. 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.
In an additional experiment, the team found elevated levels of O-GlcNAc-modified CaMKII in both hearts and brains of deceased humans who were diagnosed with diabetes, with the highest levels in the hearts of patients who had both heart failure and diabetes.
The study has been published in the journal Nature.
--ANI (Posted on 01-10-2013)