Discovery of mechanism could explain heart damage in people with diabetes

Jack Woodfield
Fri, 27 May 2016
Discovery of mechanism could explain heart damage in people with diabetes
American researchers have uncovered a molecular mechanism that is involved in diabetic cardiomyopathy, a form of heart damage found in people with diabetes.

Diabetic cardiomyopathy is when the heart muscle becomes damaged which prevents the heart from properly circulating blood, leading to heart failure. People with diabetes have an increased risk of developing cardiovascular disease; diabetic cardiomyopathy is identified when unhealthy changes occur in the heart.

Scientists at The University of Texas Medical Branch (UTMB) at Galveston led a nationwide study team that investigated which molecular mechanisms are responsible for the development of diabetic cardiomyopathy.

Researchers long discovered that when the RNA - which helps makes the protein building blocks of cells - is spliced, it generates mRNA, but splicing mistakes in the body can produce harmful proteins that are associated with a variety of human diseases.

Previous studies found that incorrect splicing leads to elevated levels of a splicing regulator called RBFOX2 in the heart tissue of people with diabetes.

In this new study, the research team discovered that RBFOX2 binds to 73 per cent of the RNA that are spliced wrongly in diabetic heart tissues. This alternative splicing adversely affects gene expression, which is important for molecular metabolism, protein trafficking and calcium handling in heart muscle tissue.

Lead author N. Muge Kuyumcu-Martinez, UTMB, said: "We discovered that RBFOX2 function is disrupted in diabetic hearts before cardiac complications are noticeable and RBFOX2 dysregulation contributes to abnormal calcium signalling in the heart."

By identifying RBFOX2 as an important contributor to diabetes-related complications, Kuyumcu-Martinez and colleagues hope this can help them learn how it becomes dysregulated.

This could lead to new tools to diagnose, prevent or treat diabetic cardiomyopathy in the future.

The study is published in the journal Cell Reports.
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