Despite decades of study, scientists remained unsure as to how insulin binds to the insulin receptor on the surface of cells to allow them to take up sugar from the blood and transform it into energy. Now, a definitive answer has now been found with a team of scientists capturing the first three-dimensional images of insulin “docking” to its receptor. It is hoped that the new knowledge can be exploited to develop new and improved insulin medications to treat type 1 and type 2 diabetes.
The international research team was led by scientists from the Walter and Eliza Hall Institute (WEHI) in Melbourne, with collaborators from La Trobe University, the University of Melbourne, Case Western Reserve University, the University of Chicago, the University of York and the Institute of Organic Chemistry and Biochemistry in Prague.
Using the MX2 microcrystallography beamline at Australia’s Synchrotron, the researchers were able to obtain highly detailed, three-dimensional x-ray images of insulin and the insulin receptor to reveal how the two interact.
“We have now found that the insulin hormone engages its receptor in a very unusual way,” Associate Professor Mike Lawrence from the WEHI said. “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'.”
The researchers believe the new knowledge will allow them to generate new types of insulin, a process that has been hampered by the inability to see how insulin docks to the insulin receptor in the body.
“Insulin is a key treatment for diabetics, but there are many ways that its properties could potentially be improved,” Associate Professor Lawrence said. “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.”
The research team's paper is published in the journal Nature.
Associate Professor Lawrence details the discovery in the video below.
Source: Walter and Eliza Hall Institute
