One of the first signs of type 2 diabetes is muscle insulin resistance, when muscles stop responding to the hormone insulin. To understand how muscle insulin resistance occurs, Dr Andy Wilhelmsen studied human muscle cells grown in the lab. His techniques have the potential to replace animal experimentation and provide a non-animal research approach in the study of diabetes. 

The Problem 

When we eat, food is broken down and the levels of sugar (glucose) in our blood rises. To keep the amount of sugar in the blood at the right level, the pancreas produces a hormone called insulin. Insulin tells cells around the body – particularly muscle, liver, and fat cells – to take up more glucose, to reduce blood sugar levels.  

Around four million people in the UK are livingwith diabetes. This means their blood sugar can be too high, which can lead to serious health problems. 90% of these people have type 2 diabetes, where either the pancreas is unable to produce enough insulin, or the body does not respond to insulin as it should. When muscle cells stop responding to insulin, it is called ‘muscle insulin resistance’, and is one of the first signs of type 2 diabetes.  

Research into diabetes and muscle insulin resistance has often used animals and animal-derived cells. Although animal research was used to develop the first insulin therapies to treat diabetes which dramatically improved survival rates, animal muscles and human muscles do not behave in the same way. We still don’t know exactly how muscle insulin resistance occurs in humans. We need to find new ways to study muscle insulin resistance and type 2 diabetes that are more relevant to humans.  

“With greater knowledge and technologies, we are able to move away from using animals and animal cells and focus on models of the body that use human cells in our experiments.”

Dr Andy Wilhelmsen.  

The Project 

During his PhD project at the FRAME Lab, Dr Andy Wilhelmsen used a different approach to study insulin resistance in human muscles. He grew human muscle cells in a petri dish from small muscle samples donated by volunteers, recreating many features of real human muscles.  

In his project, Andy used his ‘muscle in a dish’ to investigate a protein called myostatin, which is known to limit muscle growth, and may be involved in muscle insulin resistance.  

There are many factors which increase a person’s risk of developing type 2 diabetes, including older age and being obese. To investigate how myostatin might be linked to type 2 diabetes, he studied muscle cells taken from people of different ages, with and without obesity. He found that it is obesity, not age, which increases myostatin in muscles. Given that obesity is a strong risk factor for type 2 diabetes, this supports the link between myostatin and muscle insulin resistance.  

The next step with the project is to investigate how exactly fat tissue in the body communicates with muscle cells to increase myostatin. To study this in the lab, Andy will take samples of fat tissue donated by human volunteers with and without obesity and use these fat tissue samples together with the muscle samples. Doing this will help Andy to identify what messages the fat tissue are sending to the muscles, and what effects these have.  

The Potential 

Andy’s research is helping to uncover whether myostatin has a role to play in muscle insulin resistance in humans, and the development of type 2 diabetes. By creating a model of type 2 diabetes based on human cells, the findings could be more directly applied to human disease. Ultimately, this could find new non-animal ways to diagnose and treat type 2 diabetes, and reduce the significant burden faced by millions of people.  

 Dr Andrew Wilhelmsen completed his PhD research at the FRAME Lab in 2022.