Recent innovations in microscopy and other fields could help researchers better understand a type of receptor in the body — potentially leading to more effective treatments for type 2 diabetes.
Recent research spearheaded by investigators from the University of Birmingham, in the United Kingdom, has used innovative technology to uncover more information about a key molecule, and this new understanding could have applications in the treatment of metabolic diseases.
More specifically, the team focused on obtaining better images of the glucagon-like peptide-1 receptor (GLP1R), a receptor protein that is present on specialized cells — called beta cells — of the pancreas and on certain brain cells that produce insulin.
Insulin is a hormone that plays a key role in the regulation of blood sugar levels, and impairments in insulin production are the main characteristic of type 2 diabetes.
GLP1R can help regulate blood sugar by stimulating the specialized cells to produce more insulin. That is why the molecule has been a target for diabetes therapy.
However, so far, many of GLP1R’s various characteristics and functions have remained unclear because the receptor’s minute size has made it difficult to image.
Now, the team from the University of Birmingham and other international institutions has managed to use innovative, sophisticated microscopy to learn more about GLP1R.
They explain their methods and findings in a new paper that appears in the journal Nature Communications.
In their study, the researchers used super-resolution microscopy alongside an advanced molecule-tracking technique called immunostaining and experiments in mouse models to find out more about GLP1R.
By doing so, they were able to discover not just where, exactly, these receptors are located on cells, but also how they react to certain signal molecules.
This has allowed the team to map and present a comprehensive compilation of updated information about GLP1R, including more accurate indications about how to detect the molecule’s presence.
“Our research allows us to visualize this key receptor in much more detail than before,” notes senior study author Prof. David Hodson, from the University of Birmingham.
“Think about watching a movie in standard definition vs. 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.”
– Prof. David Hodson
The researchers emphasize that the breakthrough in visualizing GLP1R was only possible because they used an interdisciplinary approach and innovative tools.
“Our experiments, made possible by combining expertise in chemistry and cell biology, will improve our understanding of GLP1R in the pancreas and the brain,” says co-author Johannes Broichhagen, Ph.D., from the Max Planck Institute for Medical Research, in Heidelberg, Germany.
“Our new tools have been used in stem cells and in the living animal to visualize this important receptor, and we provide the first super-resolution characterization of [a molecule such as GLP1R],” he adds.
The current research, the authors note in their study paper, was made possible thanks, in part, to financial support from the research charity Diabetes UK.
Elizabeth Robertson, Ph.D., the director of research at Diabetes UK, emphasizes why a study like this is so important for the future improvement of diabetes treatments.
“The effects of type 2 diabetes are serious and widespread, so finding more effective treatments to help people manage their condition and reduce their risk of its potentially devastating complications is absolutely vital,” she says.
Robertson suggests that such findings are “trailblazing” in terms of the new pathways that they open up.
“Through innovative research like this, we can get to grips with key aspects of type 2 diabetes in unprecedented detail, and blaze a trail towards better treatments,” she goes on to note.