Scientists used crystals to uncover why the diabetes treatment glulisin works faster than insulin.
The results, 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 together with Diamond Light Source – the UK’s national synchrotron science facility.
Glulisin is a synthetic, fast-acting synthetic insulin developed by Sanofi-Aventis – with the trade name Apidra. It is used to improve blood sugar control in adults and children with diabetes.
In this new study, scientists wanted to determine the exact structure of glulisine and how that structure affects behavior in the body.
The team wanted to find out what fundamental role glulisin plays in diabetes management by studying its structure. These results could potentially lead to improved synthetic insulin for patients with fewer side effects.
To conduct the research, the team created a perfect crystal from glulisin (see picture).
The researchers then used a combination of methods to get a detailed look at the structure and function of glulisin.
Dr. Hodaya Solomon, member of the Imperial College team and joint lead author, said, “The key molecular-level comparisons between this crystal structure of glulisin and previous insulin crystal structures indicated that a unique position of glutamic acid (an amino acid), absent in other fast-acting analogues directed inwards rather than outwards. This reduces the interactions with neighboring molecules and thus increases the preference for the dimer form, which is more active for patients, allowing experts to better understand the behavior of glulisin. ”
Imperial Professor Naomi Chayen was joint lead researcher.
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 is providing novel structural information on a clinically relevant synthetic insulin, glulisine, an essential treatment for patients with diabetes.
“This information provides information about the dissociation of glulisine and can explain its rapid dissociation into dimers and monomers and thus its function as a fast-acting insulin. This new information could lead to a better understanding of the pharmacokinetic and pharmacodynamic behavior of glulisine and in turn help improve its formulation and reduce the 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
See the press release of this article