Making the heart sensitive to insulin, to treat heart failure

Targeting early extracellular matrix abnormalities to treat cardiac insulin resistance and associated dysfunction

Insulin is an important hormone that helps control blood sugar (glucose) levels. Many people with heart failure have some level of ‘insulin resistance’, which stops them metabolising glucose efficiently. Heart cells rely on energy from glucose to be able to work normally. Correcting insulin resistance in the heart is therefore of much interest as a potential treatment for people with heart failure. Dr Kang and her team at the University of Dundee believe that insulin resistance develops in the heart because of an excessive build-up of the ‘scaffold-like’ molecules – known as the extracellular matrix (ECM) - which give the heart its structure. In this project, they will study overweight mice - which are resistant to insulin – with altered levels of scaffold molecules to explore in detail how these alterations affect heart function. They will also examine how specific receptor molecules found in the ECM could be linking these processes. With these findings, they will then test whether existing and in-development drugs, which can block the build-up of ECM, can reduce insulin resistance and improve heart function in mice. This could lead to the development of this type of drug as a potential heart failure treatment in the future.