Molecular mechanisms in cardiometabolic disease: effects of diabetes on the heart

The aim of this project is to understand how diabetes causes diseases of the heart. This represents continuation of research by our group which has provided important insights into how diabetes affects heart function and worsens the impact of heart failure on ability to exercise. People with diabetes are two to three times more likely to develop diseases of the heart, including heart attack and heart failure. It is particularly important to find better strategies for prevention and treatment now, as the number of people worldwide with diabetes is predicted to increase hugely over the next 10 to 15 years.

Plan of work and impact of our studies

This project is informed by our research in cultured cells and tissues in the laboratory, and involves investigating heart failure and heart attacks in mice  that have had their genes altered to change  their susceptibility to diabetes and heart disease. We can study diabetes in mice by feeding a high energy diet or giving a drug to reduce insulin production by the pancreas. We can replicate common heart diseases in mice including heart attack, heart muscle disease (cardiomyopathy), thickening of heart muscle (hypertrophy) and heart failure by surgical procedures or by the administration of drugs. We can also investigate how impaired mobility impacts muscles in the legs by placing a tape to restrict ankle movement. By studying the effects of individual genes, our intention is to determine the molecular mechanisms by which diabetes causes heart disease and affects the body’s muscles, so that we can develop new ways of prevention, monitoring and treatment for people with diabetes and heart disease. 

Animal welfare

Genetic alterations in this project are used as a tool to investigate the molecular pathways linking diabetes with heart disease. They are not themselves expected to cause significant overt adverse effects. In some cases, mice will undergo surgery to mimic diseases similar to those seen in humans (for example placing a stitch around an artery to cause a heart attacks or thickening of the heart muscle). All animals receive anaesthesia during surgery and pain relief afterwards to minimise discomfort. As in humans, some mice may die after the development of heart disease. However, in the majority of cases we can use sophisticated imaging equipment to acquire as much information as possible over time before severely-affected animals are humanely killed.

Non-technical summary 

Read a non-technical summary of molecular mechanisms in cardiometabolic disease: effects of diabetes on the heart (PDF).

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