Scientists from the UC Davis Health System have identified a biological connection between diabetes and heart disease, which may describe why diabetes patients have an enhanced risk for heart disease. This is in accordance to a research published in the journal Nature. The scientists discovered that when blood sugar levels are unusually excessive, this triggers a biological pathway that leads to abnormal heartbeats – a situation called cardiac arrhythmia – that is connected to heart failure and unexpected cardiac death.
With respect to the World Heart Federation, individuals who experience from diabetes are two to four times more probably to develop cardiovascular disease, in comparison with individuals who do not have diabetes. The American Heart Association states that about 65% of diabetes patients die from heart disease or stroke, focusing the need for new research searching at links between the situations.
For this research, UC Davis scientists, alongside collaborators at the Johns Hopkins University School of Medicine, performed a set of studies to figure out any biological factors as to why diabetes patients are at greater risk of cardiovascular disease.
O-GlcNAc-modified CaMKII a trigger of arrhythmias
The studies involved detailed molecular research in rat and human proteins and tissues, calcium imaging in isolated rat cardiac myocytes (cells found in muscle tissues) that were subjected to high glucose, as well looking at whole heart arrhythmias with optical mapping within isolated hearts and live diabetic rates.
Their discoveries revealed that moderate to high blood glucose levels, identical to those found in diabetics, activated a sugar molecule known as O-GlcNAc (O-linked N-acetylglucosamine) in heart muscle cells to combine a particular site on a protein known as CaMKII (calcium/calmodulin-dependent protein kinase II).
With respect to the scientists, CaMKII has a significant part in controlling normal calcium levels, electrical task and the pumping activity of the heart. But they identified its interaction with O-GlcNAc triggered CaMKII to over activate, resulting in pathological adjustments in the calcium signalling system it controls. This activity brought on completely active arrhythmias within minutes.
However, the scientists say the arrhythmias were avoided by suppressing CaMKII and its binding to O-GlcNAc. A further research, which involved examining the hearts and brains of deceased humans who had diabetes, unveiled high levels of O-GlcNAc-modified CaMKII. The maximum levels were identified in individuals who experienced from both heart failure and diabetes.
Study author Gerald Hart says, “Since O-GlcNAc is directly made from glucose and assists as a major nutrient sensor in managing most cellular processes, it is perhaps not surprising that connection of this sugar to proteins is growing as a significant molecular mechanism of glucose toxicity in diabetes,” .
Prof. Hart notes that these discoveries will definitely lead to development of therapies for diabetic cardiovascular disease and possible therapeutics for glucose toxicity in other tissues impacted by diabetes, such as the nervous system, the kidney and the retina.