Designing a new drug target to reduce high blood sugar and blood vessel damage in diabetes

RABEP2 is a novel GSK3 substrate that represents a single therapeutic target to reduce both hyperglycemia and microvascular disease in diabetes

People with diabetes are at an increased risk of heart and circulatory conditions because of damage to blood vessels caused by high blood sugar (glucose) levels. Small vessel disease (microvascular disease) is a complication of diabetes and can lead to heart attack, blindness, dementia, and kidney failure. In Small vessel disease the small arteries become thick and stiff and reduce in number, preventing adequate blood flow to tissues e.g. the heart muscle. In a BHF-funded project, Professor Calum Sutherland discovered that two proteins (RABEP2 and GSK3) interact with each other in the heart. These two proteins are known to be involved in two processes, namely, glucose transport from blood into cells (reducing blood sugar levels) and the function, growth and repair of blood vessels. Professor Sutherland believes that disrupting this interaction causes both high blood sugar and small vessel disease. So, repairing this interaction with a specifically-designed drug could reduce blood sugar levels in addition to maintaining the health of blood vessels. In this project, the team will test these ideas by studying genetically-engineered mice to see how interfering with the RABEP2–GSK3 interaction affects the development of diabetes and microvascular disease. Establishing a single interaction as a target for a drug could help improve blood sugar levels and reduce damage to blood vessels which could have major benefits for people with diabetes.