The aim of this project is to understand how diabetes causes diseases of the circulation. This represents continuation of research by our group which has provided important insights into how resistance to the effects of insulin leads to impaired function of blood vessels.
Rationale
People with diabetes are two to three times more likely to develop diseases of the circulation – including heart attack, stroke and lower limb arterial disease. 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 circulatory diseases in mice that have had their genes altered to change their susceptibility to diabetes and circulatory disease.
Diabetes in mice can be studied by feeding a high energy diet or giving a drug to reduce insulin production by the pancreas. Common circulatory diseases can be replicated in mice – including cholesterol build up in the arteries, repair of arteries after physical injury, aneurysm and peripheral arterial disease – by carrying out surgery or administering a drug. Healing of skin wounds can also be studied, along with growth of new blood vessels and how regulation of diabetes-related genes in pregnancy can affect the placenta and foetus.
The intention is to determine the molecular mechanisms by which diabetes causes heart and circulatory disorders, to further the development of new ways of prevention, monitoring and treatment for people with diabetes and circulatory disease.
Animal welfare
Genetic alterations in this project are used as a tool to investigate the molecular pathways linking diabetes with circulatory disease and are not themselves expected to cause significant overt adverse effects. In some cases, mice will undergo surgery to mimic diseases seen in humans (for example peripheral arterial disease, aneurysms, blood vessel damage, skin wounds).
All animals receive anaesthesia during surgery and pain relief afterwards to minimise discomfort. Sophisticated imaging equipment is used to acquire as much information as possible over time and reduce the number of animals required.