• AMRF

Cardiac changes in diabetic heart disease

Diabetes can cause irreparable damage to heart muscle and researchers hope to find a new therapeutic target

Normal contraction and relaxation of the heart is controlled by rapid changes in calcium levels. Key proteins in heart muscle cells interact to move calcium ions and change calcium ion concentrations, ensuring regular heart beating.


As a result of disease or injury, these normal interactions are impaired and the heart undergoes changes collectively known as cardiac remodelling. The net result is heart damage, with less efficient blood pumping, further affecting the rest of the body.


Heart cells of non-diabetic (A) and diabetic (B) patients show overall cellular structure is notably disrupted, and Epac (red stain, white arrows) is distributed very differently

Dr Marie-Louse Ward and her team from the Department of Physiology at The University of Auckland study the effect of cardiac remodelling in people with diabetes.


Recently they showed that proteins known as “Epac” can cause alterations in calcium regulation inside heart tissue cells. They now hold an AMRF grant to examine the role of Epac in human heart diabetic disease.


They hypothesise that it may be the prolonged or over-activation of these Epac proteins that results in changes to the heart’s ability to synchronise contraction and relaxation. Epac may therefore represent an attractive therapeutic target to improve diabetic heart function.


She says, "We know there is a different subcellular abundance and distribution of Epac in diabetic hearts. And we know impaired calcium handling contributes to the development of diabetic heart disease. We're looking to see if the reduced contractile performance of diabetic hearts might result from disrupted energy supply, since this is also dependent on cellular calcium fluxes.


"Epac proteins are also located within the mitochondria, and therefore play a role in the energy supply that fuels heart contraction. And since we know Epac plays a role in energy supply in heart tissue, it will be hugely satisfying to tie all the pieces of this story together, and develop a robust rationale to turn Epac into a drug target to help prevent some of the worst impacts of diabetes and diabetic heart disease.


"These AMRF funds allow us to investigate those links and we're really grateful for the generosity of donors that enables us to do this work."

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