Highresolution microscopy to detect GLP-1 distribution in cells

High-resolution microscopy to detect GLP-1 distribution in cells

Scientists have examined a key receptor for the first time at high resolution - broadening understanding of how it might function, and opening the door to future improvements in treating conditions such as type 2 diabetes.

Glucagon-like peptide-1 receptors (GLP1R) are found on insulin-producing beta cells of the pancreas and neurons in the brain. The receptor encourages the pancreas to release more insulin, stops the liver from producing too much glucose, and reduces appetite. This combination of effects can helps to control blood sugar levels.

As such, GLP1R has become a significant target for the treatment of type 2 diabetes, and a range of drugs are now available that are based on it. But much remains unknown about GLP1R function because its small size makes it difficult to visualise.

An international group of scientists have now conducted a detailed examination of the receptor in living cells. Researchers used a number of techniques - including synthesis of marker compounds, immunostaining, super-resolution microscopy, as well as 'in vivo' examination of mice. They were able to label GLP1R with their developed fluorescent probes so as to show its location in the cells and its response to signal molecules.

Publishing their findings in Nature Communications, the researchers note that they now provide a comprehensively tested and unique GLP1R detection toolbox, which has updated our view of this receptor, with implications for the treatment of conditions such as obesity and type 2 diabetes.

The senior author commented: "Our research allows us to visualise this key receptor in much more detail than before. Think about watching a movie in standard definition versus 4k, that's how big the difference is. We believe this breakthrough will give us a much greater understanding of GLP1R distribution and function. Whilst this will not immediately change treatment for patients, it might influence how we design drugs in the future."

GLP1R is a member of the so-called G protein-coupled receptors (GPCRs), which play a role in many of the body's functions. An increased understanding of how they work has greatly affected modern medicine, and today, it is estimated that between one-third and one-half of all marketed drugs act by binding to GPCRs.