Lipid-induced insulin resistance and metabolic dysfunction: the role of caveolins and cavins
Increased levels of a molecule called DAG (found in dietary fat) has been shown to cause insulin resistance in muscle cells, by disrupting important signals. Increased dietary fat also appears to reduce the number of cave-like structures (formed by proteins called caveolins) on the surface of cells. The aim of this project is to investigate the connection between the cave-like structures, DAG and insulin resistance. This will improve our understanding of how insulin resistance happens in people with Type 2 diabetes, and could inform future strategies for managing and treating the condition.
Background to research
The surface of our cells are covered in cave-like structures, which are formed by cholesterol and proteins called caveolins and cavins. When these proteins don’t work properly, the cave-like structures are lost and the body’s ability to process fat and respond to insulin are disrupted. DAG, a molecule found in dietary fat, can make cells less sensitive to insulin. Professor Hundal’s team have found that increased dietary fat (and therefore higher levels of DAG) cause the ‘caves’ to be lost, and this makes the cells more susceptible to the desensitising effects of DAG.
This project aims to find out why dietary fat causes the ‘caves’ to disappear. The team will examine why a loss of the ‘caves’ causes the cells to be more susceptible to the insulin-desensitising effects of DAG. They’ll then attempt to identify whether curbing the loss of the ‘caves’ could help to prevent insulin resistance caused by high levels of dietary fat and DAG. To answer these questions, they will be looking specifically at how proteins interact with each other on a molecular level. They’ll then test their theories on human cells and an animal model of diabetes.
Potential benefit to people with diabetes
Obesity is the leading cause of Type 2 diabetes, and while we know that dietary fat can lead to insulin resistance, the underlying reasons why are not completely clear. This project will improve our understanding of the role fat plays in insulin resistance, and could inform future strategies for managing and treating Type 2 diabetes. £60,000 pledged by Pethybridge Trust