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A new paper from the Heather and Tyler groups has uncovered the mechanism responsible for reduced energy in the hearts of patients with type 2 diabetes and revealed a new therapeutic strategy to reverse the energy deficit.

Graphical abstract showing increased energy levels in the heart when mitochondrial deacetylase SIRT3 activator "honokiol" is administered to the diabetic heart, compared to lower levels in the research control group.

Patients with type 2 diabetes have less energy within their hearts, resulting in less energy to power the pumping of the heart. However, the mechanisms responsible for this energy deficit, and whether therapies could be used to reverse this, have so far been unknown. 

The diabetic heart is a battery half empty - Prof Lisa Heather

New research led by Associate Professor Lisa Heather shows that early on in the development of diabetes, the cardiac mitochondria, known as the cellular power stations, work more slowly. This is due to a post-translational modification of a large number of mitochondrial enzymes. Mitochondrial proteins become hyperacetylated, which decreases the ability of the heart to use fuel for energy production. 

The team then demonstrate that a mitochondrial deacetylase SIRT3 activator, called honokiol, when administered in diabetes is able to reverse the hyperacetylation, speed up mitochondrial function and increase the amount of energy within the heart.

Prof Lisa Heather said: "By identifying the mechanisms and a way to reverse it, honokiol provides a therapeutic route to 'recharge the heart's battery' in diabetes."

"Ultimately, strategies to improve cardiac metabolism and energy generation in type 2 diabetes may provide much needed routes to decrease mortality from cardiovascular disease, the leading cause of death, in diabetes."

 

The full paper "Rescue of myocardial energetic dysfunction in diabetes through the correction of mitochondrial hyperacetylation by honokiol" is available to read in JCI Insight.

DPAG team members who have contributed to this paper include Matthew Kerr, Dr Jack Miller, Dr Kerstin Timm, Claudia Montes Aparicio and Professor Damian Tyler.

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