A better view of proteins linked to diabetes paves the way for new therapies

Diabetes is a chronic disease that affects approximately 463 million adults in 2019, or one in 11 adults worldwide. These figures, taken from the 9^and edition of The Diabetes Atlas of the International Diabetes Federation, predict that the adult population with diabetes will reach 578 million in 2030 and around 700 million in 2045. However, new research could help scientists develop new therapies to treat type 2 diabetes. experts from the University of Birmingham (UK) and the Max Planck Institute for Medical Research (Germany), carried out a detailed examination of a crucial high-resolution receptor. The results of their study were published in the journal NatureCommunications.

Glucagon-like peptide-1 (GLP1R) receptors are found on pancreatic beta cells and neurons that produce insulin. This receptor encourages the production of insulin in the liver, stops excessive production of glucose and reduces appetite, thereby regulating blood sugar. GLP1R is important for the treatment of type 2 diabetes and many drugs are based on it. Despite everything, the medical profession knows little about its function, because of its small size which makes its visualization difficult.

The study of the key receptor

For their study, the researchers used several techniques, such as immunolabeling (a technique to mark certain proteins that would be difficult to see under a microscope), the synthesis of marker compounds, super-resolution microscopy and in-vivo examination. of mouse. Using fluorescent probes, scientists were able to tag GLP1R to see its location on cells and its response to signal molecules. In fact, this research has allowed the team to develop a “toolbox” capable of detecting GLP1R, which could help in particular to better treat obesity and type 2 diabetes.

GLP1R is a member of G-protein-coupled receptors (GPCRs), which play an important role in many body functions. The role of GPCRs is preponderant since they constitute the largest family of membrane receptors in mammals, to such an extent that more than half of the drugs we take act on GPCRs.

Using these combinations of techniques, the team was able to better visualize the receiver. According to David Hodson, professor of cellular metabolism at the University of Birmingham, this will facilitate an in-depth understanding of the distribution and function of GLP1R. “While this won’t immediately change how patients are treated, it could influence how we design medicines in the future.”

Make a big difference

Johannes Broichhagen, head of the study group at the Max-Planck Institute for Medical Research, agrees. “The experiments that were conducted by combining expertise in chemistry and cell biology, will lead to a better understanding of GLP1R in the pancreas and brain. Our new tools have been used in stem cells and in living animals to visualize this important receptor. We provide the first super-resolution characterization of an GPCR. Importantly, our results suggest a degree of complexity that was not easily appreciable with previous approaches.”

Diabetes can seriously affect quality of life and can even be fatal if not managed properly. Since many patients are in middle- and low-income countries, this is a serious risk. Dr Elizabeth Robertson, director of research at Diabetes UK, which partially funded the study, said the findings could help people better manage the disease and reduce the risk of its serious complications. “With innovative research like this, we can tackle key aspects of type 2 diabetes in unprecedented detail and pave the way for better treatment.”