Scientists have used crystals to reveal why the diabetes treatment glulisine is faster acting than insulin.
The findings, published today in Scientific Reports, could open avenues for improved diabetes treatments.
The study was carried out by Imperial College London, and the Universities of Nottingham and Manchester, along with the Diamond Light Source - the UK's national synchrotron science facility.
Glulisine is a synthetic rapid-acting synthetic insulin developed by Sanofi-Aventis - with a trade name of Apidra. It is used to improve blood sugar control in adults and children with diabetes.
In this new study, scientists set out to establish the exact structure of glulisine, and how this structure might affect the way it behaves in the body.
The team aimed to establish, what fundamental role glulisine plays in diabetes management by examining its structure. These findings could potentially lead to an improved synthetic insulin for patients, with fewer side effects.
To carry out the research, the team created a perfect crystal of glulisine (see image).
The researchers then applied a combination of methods to provide a detailed insight into the structure and function of glulisine.
Dr Hodaya Solomon, a member of the Imperial College team, and joint first author said: “The key molecular level comparisons between this crystal structure of glulisine and of previous insulin crystal structures showed that a unique position of the glutamic acid (an amino acid), not present in other fast-acting analogues, pointed inwards rather than to the outside surface. This reduces interactions with neighbouring molecules and so increases preference of the more-active-for-patients dimer form, giving the experts a better understanding of the behaviour of glulisine”.
Imperial's Professor Naomi Chayen was joint senior author of the research.
Dr Gary Adams Associate Professor and Reader in Applied Diabetes Health at the University of Nottingham, and lead author of the study, said: “For the first time, our research provides novel, structural information on a clinically relevant synthetic insulin, glulisine, which is an important treatment for those patients presenting with diabetes.
“This information sheds light on the dissociation of glulisine and can explain its fast dissociation to dimers and monomers and thereby its function as a rapid-acting insulin. This new information may lead to a better understanding of the pharmacokinetic and pharmacodynamic behaviour of glulisine and, in turn, might assist in improving its formulation and reducing side effects of this drug.”
The study was funded by the Independent Diabetes Trust.
'Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques' is published in the journal Scientific Reports
Adapted from a press release from The University of Nottingham
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