Deciphering a surprising discovery in type 2 diabetes

Examining the mechanisms and pathophysiological implications of the phenotypic switch in the endothelium of mice with endothelial cell specific IGF-1 and insulin resistance

Type 2 diabetes is a major global challenge. The condition can have a wide range of health consequences, including causing damage to blood vessels and raising the risk of a heart attack. Type 2 diabetes occurs when the body’s cells can’t respond properly to the hormone insulin. Insulin should ‘unlock a door’ into our cells, so that glucose (sugar) can enter and be used as a fuel. But in type 2 diabetes either cells become resistant to insulin or not enough insulin is made, so glucose is locked out of cells and blood sugar levels increase. This Leeds team has been researching the effect of diabetes on blood vessels. They have genetically engineered a mouse so that the cells in the lining of blood vessels – known as the endothelium - could not respond to insulin. This led to a surprising discovery; these mice had lower blood sugar levels, not higher blood sugar levels as expected. The diabetic endothelium appeared to be sending out chemical signals that made the rest of the body better at responding to insulin. In this project they will go further to decipher the biological processes behind this discovery. The researchers believe that these findings will change the way we think about the endothelium in type 2 diabetes, and could pave the way for a new approach to treatment.