Glucagon and obesity-related disease

What we do

Glucagon and related natural hormones are powerful mediators of human metabolism. We aim to understand how aberrant glucagon signalling affects the development of obesity-related diseases.

Why it is important

Steatotic “fatty” Liver Disease (SLD) affects 1 in 3 UK adults: of these, 1 in 20 will progress to liver failure and/or liver cancer. Most of the people affected also suffer from obesity and many have Type 2 diabetes. Unfortunately, SLD is often not recognised in the early stages. Furthermore, there are very few pharmaceutical treatments available for SLD. 

Glucagon is a powerful hormone that reduces liver fat and increases blood sugar. By better understanding how glucagon works in health and disease, we hope to safely harness its actions to help develop new medicines for people with SLD and related problems. 

How it can benefit patients

Through this work we hope to improve outcomes for people with obesity-related disease.

Summary of current research

‘Glucagon resistance’ in people with SLD

We are developing new techniques to measure glucagon signalling in people with SLD. We are interested in understanding how resistance to glucagon develops, who it affects and whether it can be reversed by weight loss.  

Mechanism of ‘glucagon resistance’

We are investigating whether changes in the shape of the glucagon receptor are responsible for impaired glucagon signalling. We study how this can be modified by other molecules e.g. cholesterol. We are also studying the effect of genetic changes on the shape and function of the glucagon receptor.

Using blood markers of glucagon signalling to predict SLD

We are using population data to understand if impaired glucagon signalling can be detected by blood tests, and if this could help us diagnose early stages of SLD.

Health-related quality of life in people with obesity-related disease

We use registry data to understand how health-related quality of life may suffer in people with obesity-related disease and how it changes following weight loss. By studying this alongside other clinical outcomes we aim to help people make decisions between different types of treatment for obesity.