Project summary
Tiny variations in our genes can affect insulin receptors, which sit on the surface of our cells and allow insulin to enter. Problems with insulin receptors affect how our body responds to insulin and can cause severe insulin resistance. Professor Semple and his student want to find out how thousands of different genetic variations affect how the insulin receptor works, and which variations contribute to insulin resistance. They hope this will make it easier to diagnose people with rare types of diabetes and help them learn more about how insulin works in all types of diabetes, paving the way to new insulins or ways of making insulin work better.
Background to research
All types of diabetes are caused by problems with insulin. When the body can’t properly use the insulin we make it’s called insulin resistance.
Cells in our bodies have a structure called the ‘insulin receptor’. An insulin receptor is like a lock on the surface of our cells. Insulin is the key that fits in this lock and allows cells to open up and take in glucose from the blood.
Some people inherit versions of genes which change the shape of the insulin receptor ‘lock’ and prevent it from working properly. This can cause a rare type of genetic diabetes, where people have severe insulin resistance. But there are tens of thousands of different gene variations that can affect the insulin receptor. And right now, it’s difficult to tell which variations are harmless and which contribute to the development of severe insulin resistance.
Research aims
Professor Robert Semple and his PhD student aim to study how tens of thousands different genetic variations affect an important part of the insulin receptor, to find those responsible for causing a problem.
To do this they’ll use cutting-edge new techniques that have only recently been invented. The gene for the insulin receptor is made up of building blocks called amino acids. They’re arranged in a very precise order, like beads on a string. Professor Semple and his team will look at changes in a specific area of this “string” and see what happens if they change the order of different amino acids. Doing this will let them identify how different variations of genes affect how the receptor is made, how it sticks to insulin and how it triggers insulin responses.
Potential benefit to people with diabetes
The findings could help us understand the genetic basis of why people develop problems responding insulin (severe insulin resistance). This knowledge could be used to help speed up diagnosis for people with a rare form of diabetes.
The researchers also hope their findings will teach us important lessons about how insulin works in people with all types of diabetes. This could help to discover ways to make new insulins or other medicines that make insulin work better.
