Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. 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

Strong performance for DPAG cardiac research at the Oxford BHF CRE Annual Symposium

Congratulations are in order for Kaitlyn Dennis, Dr Ni Li and Dr KC Park on their awards at this year's major showcase for Oxford's British Heart Foundation funded researchers.

Key cause of type 2 diabetes uncovered

Research led by Dr Elizabeth Haythorne and Professor Frances Ashcroft reveals high blood glucose reprograms the metabolism of pancreatic beta-cells in diabetes. They have discovered that glucose metabolites, rather than glucose itself, are key to the progression of type 2 diabetes. Glucose metabolites damage pancreatic beta-cell function, so they are unable to release enough of the hormone insulin. Reducing the rate at which glucose is metabolised, and these glucose metabolites build up, can prevent the effects of hyperglycaemia.

Winners of the DPAG Student Poster Day 2022 announced

"A Year of Progress" was held in the Sherrington Library on Wednesday 9 November 2022.

New study shows clinical symptoms for Alzheimer’s can be predicted in preclinical models

Establishing preclinical models of Alzheimer’s that reflect in-life clinical symptoms of each individual is a critically important goal, yet so far it has not been fully realised. A new collaborative study from the University of Oxford has demonstrated that clinical vulnerability to an abnormally abundant protein in Alzheimer’s brain is in fact reflected in individual patient induced pluripotent stem cell-derived cortical neurons.

Updating the circuit maps of the sympathetic neural network

A new review from Professor Ana Domingos’ lab and colleagues offers a fresh modern viewpoint on sympathetic neurons and their relation to immune cells and obesity.