Abnormal metabolism in type 2 diabetes, and how this affects the heart
The study of metabolism has a strong historical basis in Oxford, and in the last 20 years research in this field has undergone a renaissance. Abnormalities in cardiac metabolism have been identified in many pathologies, and have been shown to directly impair the function of the heart, accelerate disease progression and to predict mortality. Given the pivotal role of metabolism in keeping the heart contracting, a greater understanding of what metabolism can do, how this is modified in disease and whether this information can be used to develop new treatments may lead to new therapies for the heart.
Type 2 diabetes is a systemic disease of abnormal metabolism, yet the primary cause of mortality in type 2 diabetes is cardiovascular disease. Important questions remain as to what abnormal cardiac metabolism is doing to the heart in diabetes, and how it is having its effect. We are studying metabolism from 2 angles in diabetes: as a source of energy to power the heart, but also as signalling molecules that can regulate transcription, post-translational modification, and enzyme activity. Our aim is to understand how abnormal metabolism and metabolite levels are exerting their effect on the heart in diabetes. We are particularly interested in the roles played by fats and lipids within the heart, and how these may be driving the metabolic and contractile dysfunction in diabetes. Given the increasing prevalence of diabetes and metabolic syndrome in society, a greater understanding of how diabetes specifically affects the heart, and whether this can be rectified by therapy are important questions.
Our research can be divided into five key questions:
1. How is cardiac metabolism modified in type 2 diabetes? - Given that the heart can use multiple fuels to make energy, how does the balance of fuel selection change in diabetes and how is this related to the function of the heart.
2. How does type 2 diabetes affect the ability of the diabetic heart to adapt to stress?
3. What are the mechanisms regulating changes in cardiac metabolism?
4. Can these mechanisms be targeted by new pharmacological therapies to treat the heart?
For further information about our research and potential DPhil projects, please drop us an email.