Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we will assume that you are happy to receive all cookies and you will not see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Similar stories

New book expands the horizons of brain research

A pioneering book from Professor Zoltán Molnár and Yale Professors Tamas Horvath and Joy Hirsch to be released on 1 February 2022 addresses the fundamental relationship between the body, brain and behaviour.

Christoph Treiber awarded ERC Starting Grant to investigate the origins of behavioural diversity

Congratulations are in order for postdoctoral research scientist Dr Christoph Treiber who has been awarded a Starting Grant from the European Research Council. His funded project will investigate the genetic components that may contribute to diversity of brain function and behaviour.

Switch with a spring: a new model for sleep regulation

New collaborative research led by the Vyazovskiy Group has shed new light on the role of the hypothalamus in the transition between sleep and wake states.

Oxford-led research maps milestone stage of human development for the first time

Scientists have shed light on an important stage of early embryonic development that has never been fully mapped out in humans before.

Mapping uncharted networks in the progression of Parkinson’s

A major new $9 million project funded by the Aligning Science Across Parkinson’s (ASAP) initiative will map the original circuits vulnerable to Parkinson’s on an unprecedented scale. The project is a collaboration between core investigators Stephanie Cragg, Richard Wade-Martins, and Peter Magill at Oxford, Mark Howe at Boston University and Dinos Meletis at the Karolinska Institutet, as well as collaborators Yulong Li at Peking University and Michael Lin at Stanford University.