Manipulating insulin like growth factor-1 and hybrid receptor expression as a therapeutic strategy to control insulin sensitivity and cardiovascular repair (renewal)

A single molecule on the surface of blood vessel cells could determine whether a person with type 2 diabetes repairs arterial damage or suffers worsening cardiovascular disease. This matters because type 2 diabetes dramatically increases the risk of heart attacks and strokes, yet current treatments do not directly address the underlying vascular repair failure. The researchers have discovered that hybrid receptors—formed when the insulin-like growth factor-1 receptor pairs with the insulin receptor—control how blood vessels respond to insulin. In insulin-resistant states, these hybrids malfunction, reducing nitric oxide production and impairing the artery's ability to heal after injury. If this work succeeds, it could lead to a new class of drugs that selectively adjust hybrid receptor expression to restore nitric oxide bioavailability and normal vascular repair. Such treatments would target the root cause of diabetic vascular disease rather than just managing blood sugar. The potential impact is a tangible reduction in amputations, heart attacks, and strokes among the estimated 4 million people in the UK with type 2 diabetes. This is fundamental science with a clear translational path. The team has already shown in genetically modified models that manipulating these receptors can improve insulin sensitivity and arterial repair. The current programme aims to uncover the precise molecular mechanisms, a necessary step before clinical testing can begin.