Cardiovascular disease contributes to high mortality rates in patients with diabetes. However, the relation between these two devastating pairs is yet to be established.
Recently, researchers from UC Davis Health System identified a novel biochemical pathway that triggers at unusually high blood-sugar level and causes the abnormal heart rhythm (cardiac arrhythmia).
This study was published online in Nature journal on September 29, 2013. According to the authors, the results of this study help to explain the reason for higher risk of heart disease in diabetes sufferers.
One of the authors, Donald Bers, said that the molecular mechanism identified in this study may open doors to innovative ways for designing new treatment strategies, which can protect the cardiac health in diabetes patients.
According to the National Institutes of Health, diabetic patients have two to four times higher chance of developing heart diseases than non diabetics. A minimum of 65 percent diabetic sufferers may die from some form of cardiovascular disease as estimated by the American Heart Association.
For this study, UC Davis researchers in collaboration with researchers at the JHUSOM (Johns Hopkins University School of Medicine) have conducted many experiments to determine the biological reasons for the higher risk of cardiovascular disease in diabetes patients.
These experiments involved detailed molecular analysis in both rat and human tissues and proteins, calcium imaging in rat cardiac myocytes that is exposed to high glucose, and assessments of the whole heart arrhythmias with optical mapping in both isolated hearts and live diabetic rats.
The results revealed that medium to high levels of blood glucose caused O-GlcNAc sugar molecule in cardiac muscle cells to aggregate to a particular site on calmodulin-dependent protein kinase II protein.
According to Donald Bers, CaMKII plays a vital role in regulating levels of calcium, electrical conductivity and the heart beat. However, the interaction of this protein with O-GlcNAc led to long term CaMKII overactivation and triggers cardiac arrhythmia within minutes.
Researchers also observed that inhibition of CaMKII or O-GlcNAc prevented the arrhythmias. Bers also said that, the role of CaMKII in usual cardiac activity is already known; however, this study shows that O-GlcNAc is a direct CaMKII protein activator in hyperglycemic patients.
Gerald Hart, one of the collaborators, noted that the attachment of O-GlcNAc to proteins might emerge as an important molecular mechanism explaining the toxic effects of glucose in diabetes. This deduction is based on the fact that O-GlcNAc is a modified form of glucose, and it plays a major in controlling most of the cellular processes.
In a separate experiment, researchers found that O-GlcNAc at higher concentrations modified CaMKII protein in hearts as well as in the brains of patients who have diabetes. These levels were highest in patients with heart failure as well as diabetes.
Bers concluded that further investigations are needed to determine whether O-GlcNAc and CaMKII fusion also contributes in the peripheral neuropathy, a common morbidity in diabetics.
Written by: Janet Grace Ortigas