Researchers from the University of Otago have identified a key protein which triggers heart disease in people with diabetes. Their results pave the way for future development of new therapies to combat the cardiovascular complications in diabetes.
Diabetes is a chronic illness that currently affects 380 million people worldwide and this is expected to double by 2035. Over 50 New Zealanders are diagnosed every day.
The leading cause of death in people with diabetes is heart disease. Up until now, the reason for this association has been a mystery. The study, published in the International Journal of Cardiology, explains why the cells of diabetic hearts have alterations in their behaviour that begin even before cardiovascular symptoms appear.
Dr Rajesh Katare and colleagues discovered that autophagy, a normal process involving the destruction of defunct cellular components, occurs at an increased rate than normal in mice models of type-2 diabetes. The up-regulation of autophagy leads to the activation of certain proteins, triggering cell death and the loss of cardiac cells. Heart failure ensues when excessive numbers of cells die.
Katare et al. collaborated with cardiothoracic surgeons at Dunedin Hospital to confirm their laboratory-based results with those from samples of heart tissue collected from coronary bypass patients. With 35 type-2 diabetic heart samples matched to comparable non-diabetic samples, the researchers discovered for the first time that diabetic heart tissues had markedly increased autophagy compared to samples from non-diabetics.
The researchers investigated the progressive loss of cardiac cells by examining how autophagy is induced. The process of autophagy teeters between being beneficial and destructive. This fine balance depends on the timing, location and rate of autophagy, and sometimes it goes wrong. Uncontrolled autophagy contributes to the development of various diseases.
Katare et al. identified the pro-autophagy protein called Beclin-1 and suggest that it has a key role in mediating the excessive autophagy in type-2 diabetes. They propose that Beclin-1 is activated by high blood glucose – the human diabetic hearts they studied had a notable increase in this protein. Once activated, Beclin-1 is able to initiate the process of autophagy, as well as another cell death process called apoptosis.
Beclin-1 is “an extremely promising target for new treatments of diabetes-related cardiac disease” says Dr Katare.
“Given that the growing diabetes epidemic is set to create major global economic and social costs in coming decades, it is very exciting to have opened up a new research avenue that could greatly decrease the disease’s burden,” Dr Katare says.
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