Role of alternative pathways of triglyceride synthesis in determining insulin sensitivity in muscle of individuals at risk of Type 2 diabetes
Professor Zammit and his team aim to find out if enzymes that produce fat in the muscle determine whether it is 'good' fat (seen in athletes) or 'bad' fat (seen in many people with Type 2 diabetes). They will also see if altering the route by which muscle fat is produced might help to prevent or reduce insulin resistance and Type 2 diabetes.
Background to research
One of the key causes of Type 2 diabetes is a build-up of fat in the muscles, interfering with their ability to take up glucose in response to insulin. This ‘insulin resistance’ forces the pancreas to make more and more insulin in order to maintain normal blood glucose levels. Eventually the pancreas can no longer keep up and Type 2 diabetes is the result. Strangely, high levels of fat are also found in the muscle of trained athletes, who are highly sensitive to insulin. Professor Victor Zammit and his colleagues have shown that this is because there are different kinds of muscle fat, made from different molecules by two different enzymes in the muscle. They believe that an enzyme called DGAT2 produces ‘bad’ muscle fat that contributes to insulin resistance, whereas an enzyme called DGAT1 produces ‘good’ muscle fat that is stored safely for use during physical activity.
Professor Zammit and his team aim to find out if the enzymes that help to produce fat in the muscle determine whether it is 'good' or 'bad' fat, and if promoting the production of one kind of muscle fat over another might be a new way to prevent or reduce insulin resistance and Type 2 diabetes. He will use thigh muscle biopsies from people without diabetes, people at risk of Type 2 diabetes and endurance athletes to find out if the ratio of enzymes DGAT1 and DGAT2 in muscle contributes to the risk of Type 2 diabetes. Using cells from these biopsies in the lab, they will also find out how fat is made and if altering the enzyme ratio affects muscle sensitivity to insulin.
Potential benefit to people with diabetes
This research will find out if altering the route by which fat is produced in muscle can reduce insulin resistance. If it is successful, it could lead to new treatments to block DGAT2 and inhibit the production of bad fat in order to reduce the risk of Type 2 diabetes and slow its progression. This would help to overcome current treatment strategies aimed at improving muscle insulin sensitivity, which can have side effects.