Insulin’s molecular handshake caught in the act

Insulin has been the focus of intense research efforts ever since its isolation and characterisation last century. Yet it has taken until today for us to get a clear picture of how the peptide docks with cells, thus enabling them to take up sugar.

The work, led by Associate Professor Mike Lawrence, Professor Colin Ward and Dr John Menting from the Walter and Eliza Hall Institute used the Australian Synchrotron to shed light, as it were, on the activity of insulin.

The finding could pave the way for developing new types of insulin for treating both type 1 and type 2 diabetes.

The team employed the powerful MX2 microcrystallography beamline at the Synchrotron, run by Dr Tom Caradoc-Davies, to image how insulin conducts its ‘molecular handshake’ with other cells.

The team found that both insulin and the insulin receptor change their shape in order to bind with each other, and understanding the dynamics of this interaction could reveal why sometimes the process breaks down.

It could also lead to new types of insulin that might be easier to administer, such as by tablet form rather than via injections.

“Understanding how insulin interacts with the insulin receptor is fundamental to the development of novel insulins for the treatment of diabetes,” said Lawrence.

“Until now we have not been able to see how these molecules interact with cells. We can now exploit this knowledge to design new insulin medications with improved properties, which is very exciting.”

The micro-focus beamline at the Australian Synchrotron has a highly-focused x-ray beam that is particularly useful for gathering diffraction data from very small crystals such as those used in this study.

It is also thousands of times brighter than laboratory x-ray sources, enabling the experiment to be completed in minutes rather than weeks.

“What made the insulin work possible for us was being able to make regular visits to a local synchrotron instead of having to travel overseas,” said Lawrence.

“It’s difficult to grow crystals of insulin docking with its receptor, but frequent synchrotron visits meant we could optimise the crystal preparation methods and the experimental settings rather than guessing what might work.”

The study was published today in Nature.

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