Could Insulin ‘Docking’ Lead To Better Diabetes Treatments?

The wellbeing of diabetes sufferers may be improved, thanks to a landmark discovery about how insulin docks on cells, as this could lead to improved types of insulin for treating the wellness of people with both type 1 and type 2 diabetes. The researchers have managed to capture the intricate way in which insulin uses the insulin receptor to bind to the surface of cells for the first time. It is necessary for insulin to bind in this way, as otherwise the cells can’t take up sugar from the blood as energy.

The study was published in the journal Nature, and was led by Associate Professor Mike Lawrence, Professor Colin Ward and Dr John Menting of the Walter and Eliza Hall Institute and used the Australian Synchrotron in Melbourne. For the last 20 years, the way in which insulin binds to the insulin receptor has remained a mystery to scientists, and according to Lawrence, from the institute’s Structural Biology division, the team has made an important discovery because ‘Understanding how insulin interacts with the insulin receptor is fundamental to the development of novel insulins for the treatment of diabetes’.

Lawrence added that a large part of the team’s success was due to the Australian Synchrotron’s MX2 microcrystallography beamline; ‘If we did not have this fantastic facility in Australia and their staff available to help us, we would simply not have been able to complete this project’. The project collaborators cam from Case Western Reserve University, the University of Chicago, the University of York and the Institute of Organic Chemistry and Biochemistry in Prague, and this collaboration was ‘essential’, says Lawrence. ‘No one laboratory has all the resources, expertise and experience to take on a project as difficult as this one.’

Lawrence explained, ‘We have now found that the insulin hormone engages its receptor in a very unusual way. Both insulin and its receptor undergo rearrangement as they interact – a piece of insulin folds out and key pieces within the receptor move to engage the insulin hormone. You might call it a ‘molecular handshake’.’

He concluded by saying ‘This discovery could conceivably lead to new types of insulin that could be given in ways other than injection, or an insulin that has improved properties or longer activity so that it doesn’t need to be taken as often. It may also have ramifications for diabetes treatment in developing nations, by creating insulin that is more stable and less likely to degrade when not kept cold, an angle being pursued by our collaborators. Our findings are a new platform for developing these kinds of medications.’