Targeting islet G-protein-coupled receptors for type 2 diabetes therapy

The majority of people with diabetes have type 2 diabetes (T2D), where hyperglycaemia occurs because the islet β-cells are unable to secrete enough insulin, usually in the context of insulin resistance that arises because of fat mass expansion. There are a range of pharmacotherapies in current use to treat T2D and pharmaceutical companies are actively engaged in the development of novel therapies for better glucose control. Ligands that target G-protein-coupled receptors (GPCRs) are obvious candidates because they are used successfully for a wide range of disorders and GLP-1 receptor agonists, which are a relatively recent class of diabetes therapy, have proved to be very effective in treating T2D. We provide here an overview of current successes, some drawbacks and future possibilities for GPCR-based T2D therapies.