Dr Ben Jones
Imperial Post-Doctoral, Post-CCT Research Fellowship (IPPRF)
Tissue- and genotype-specific effects of biased GLP-1 receptor agonism in type 2 diabetes
Developing new treatments for type 2 diabetes
The glucagon-like peptide-1 receptor (GLP-1R) is a protein molecule that plays an important role in controlling blood glucose (sugar) levels. Several drugs have already been developed that target the GLP-1R and are used for the treatment of type 2 diabetes. In my previous research I developed new GLP-1R-targeting drugs with unusual properties, in that they were particularly effective for helping the body produce the hormone insulin, which controls blood glucose, but were less likely than standard drugs to cause nausea, which is the main side effect of this drug class. These new drugs, termed “biased agonists”, are therefore a potentially new and exciting way to improve the treatment of type 2 diabetes. In the project funded through my IPPRF award I am planning to investigate in detail how exactly these GLP-1R biased agonists show their interesting effects. This will involve studying different systems such as how they are able to access the brain, and how they might stimulate insulin release from the pancreas.
Moreover, some people are more affected than others by GLP-1R drug side effects, whereas some people are less affected but also don’t seem to derive the benefits either. I predict that this is related to natural genetic differences in the makeup of the GLP-1R molecule which affect how the drug is able to interact with it. I am planning to test this in the lab by generating cell models that carry different “variant” GLP-1Rs. Ultimately this may be useful in knowing in advance whether different individuals will over- or under-respond to GLP-1R drugs, which will help with selecting the best treatment.