An international collaboration co-led by researchers at the Walter and Eliza Hall Institute has made a discovery that could make therapeutic insulins more effective by better mimicking the way insulin works in the body. The findings could improve treatments for diabetes, to that disease of the lives of millions of people worldwide.

The study was published in Nature Communications. The study reveals the first definitive 3-D image of how insulin successfully interacts with its receptor to 'gatekeeper' for transmitting information into cells in a process that is crucial for instructing cells to lower blood sugar levels in the body.

Understanding exactly what this process looks like could inform the design of faster-acting and longer-lasting insulin therapies.

The research was co-led by Associate Professor Mike Lawrence from the Walter and Eliza Hall Institute, in collaboration with teams led by Dr. Matthias Dreyer from the pharmaceutical company Sanofi-Aventis Deutschland GmbH and Dr. Christoph Müller at the European Molecular Biology Laboratory ( EMBL), both based in Germany.

Associate Professor Lawrence said he was thrilled to have resolved to insulin triggers cells to lower blood sugar levels. It is well established that insulin instructs cells to lower blood sugar levels in the body by binding to a receiver that is located on the cell surface.

Associate Professor Lawrence said the problem was that no one knew precisely what was occurring during the interactionCurrent insulin therapies are sub-optimal because they have been designed without this missing piece of the puzzle.

Together with our collaborators in Germany, we have produced the first definitive 3-D image of the way in which insulin binds to the surface of cells to successfully transmit the vital instructions needed for taking up sugar from the blood. 

Associate Professor Lawrence said the outcome of the collaboration between structural and cell biology experts from the Institute, working together with both cryo-electron microscopy specialists at EMBL in Heidelberg and an insulin receptor specialist from the University of Chicago.

We Knew That underwent physical change insulin That signaled ITS successful connection With its receptor on the cell surface. Takeup sugar from the blood. Indicated its successful relationship with its receiver on the cell surface.

But we had never seen the reported changes that occurred in the confirming that insulin had successfully delivered the message to the cell to take up sugar from the blood. It was at that point we knew the information needed to develop improved insulin therapies that could ensure cells would respond correctly and carry out the necessary functions to lower blood sugar levels.

Optimal therapies

Associate Professor Lawrence said the findings meant it would be possible to design insulin therapies that could mimic more closely the body's Going pharmaceutical companies will be able to use our data as a 'blueprint' for designing therapies that optimize the body's uptake of insulin.