Recent advances in microscopy and other fields may help researchers better understand a type of receptor in the body— potentially leading to more successful type 2 diabetes treatments.
Recent research led by researchers at the University of Birmingham, United Kingdom, has used innovative technology to discover more knowledge about a main molecule, and this new understanding could have implications in metabolic disease care.
More precisely, the team focused on obtaining better images of the glucagon-like peptide-1 receptor (GLP1R), a receptor protein that is present on specialized pancreatic cells — called beta cells — and on certain insulin-producing brain cells.
Insulin is a hormone which plays a key role in regulating blood sugar levels and the main characteristic of type 2 diabetes is impairments in insulin production.
By stimulating the specialized cells to make more insulin, GLP1R can help regulate blood sugar. For this reason the molecule was a target of diabetes therapy.
However, many of the different characteristics and functions of GLP1R have remained unclear so far, because the minute size of the receptor made it difficult to picture.
Now, the University of Birmingham team and other international institutions have managed to use sophisticated, innovative microscopy to learn more about GLP1R.
Their methods and findings are explained in a new paper that appears in the journal Nature Communications.
Possible effect on Drug design in the future
The researchers used super-resolution microscopy in their analysis alongside an innovative molecule monitoring technique called immunostaining, and mouse model experiments to find out more about GLP1R.
This has allowed them to discover not only where these receptors are located on cells, but also how they respond to certain signal molecules.
This has allowed the team to map and present a detailed collection of updated GLP1R information including more specific indications on how to detect the presence of the molecule.
“Our work enables us to imagine this primary receptor in much more detail than before,” says senior study author Prof. David Hodson, from Birmingham University.
“Think about watching a film in standard versus 4 K resolution, that’s how big the gap is. We believe that this finding will give us a much greater understanding of the delivery and function of GLP1R. While this won’t change care for patients immediately, it could impact how we develop drugs in the future.”
– Prof. David Hodson
The researchers emphasize that the GLP1R visualization breakthrough was only possible because they used an interdisciplinary approach and innovative methods.
“Our findings, made possible by integrating knowledge in chemistry with cell biology, will improve our understanding of GLP1R in the pancreas and brain,” says co-author Johannes Broichhagen, Ph.D., of the Max Planck Institute for Medical Research, Heidelberg, Germany.
“Our new tools have been used for visualizing this essential receptor in stem cells and in the living animal and we provide the first super-resolution characterization of[ a molecule like GLP1R],” he adds.
The current research, the authors note in their study paper, was made possible thanks partly to financial support from the Diabetes UK research charity.
Elizabeth Robertson, Ph.D., Diabetes UK’s director of research, underlines why such a study is so critical for the potential advancement of diabetes therapies.
“The consequences of type 2 diabetes are severe and common, so it is absolutely vital to find more successful treatments to help people manage their disease and reduce their risk of its potentially devastating complications,” she said.
Robertson says that results like that are “trailblazing” in terms of the new directions they open up.
“We can get to grips with key aspects of type 2 diabetes in unparalleled depth through groundbreaking work like this, and pave a trail for better treatments,” she goes on to say.
