Scientific reports (2021). DOI: 10.1038 / s41598-021-81251-2 “width =” 685 “height =” 364 “/> IGlu dimer with the double axis (green arrow), A-chain is colored light gray, B-chain is colored light blue, C. Chain in dark gray and D chain in purple. Image created with Chimera v1.8.1 cgl.ucsf.edu/chimera/. Credit: Scientific Reports (2021). DOI: 10.1038 / s41598-021-81251-2
For the first time, scientists have come up with an accurate, atomic-level explanation of why glulisine – a drug commonly used to treat diabetes – works faster than insulin.
The results, published today in Scientific Reports, could be beneficial for diabetic patients to ensure better insulin can be developed for future treatment.
The study was carried out by experts from the Universities of Nottingham and Manchester and Imperial College London 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 gluisin and how that structure affects physiological behavior.
The team wanted to determine the fundamental role gluisin plays in the treatment of diabetes by examining the structure. These results could potentially lead to improved synthetic insulin for patients with fewer side effects.
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, which is an important treatment for patients with diabetes .
“This information provides information about the dissociation of glulisine and may explain its rapid dissociation into dimers and monomers and thus its function as a fast-acting insulin. This new information may lead to a better understanding of the pharmacokinetic and pharmacodynamic behavior of glulisine help to improve the formulation and reduce the side effects of this drug. “
To conduct the research, the team created a perfect crystal from glulisin. 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 there is a unique position of glutamic acid (an amino acid) that is present in other fast-acting ones Analogue is absent and points 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, giving experts a better understanding of the behavior of glulisine. “
John Helliwell, Professor Emeritus of Chemistry at the University of Manchester and one of the authors of the paper, said: “An unexpected finding was that the glulisine formulation is documented as a zinc-free insulin analogue due to its rapid absorption action. Insulin crystallography has shown that zinc is responsible for hexamer formation by The new crystal structure of glulisine showed zinc being bound by three histidine amino acids in the same way as in native insulin. This finding must mean that traces of zinc ions are present in the trade, as supplied, for further optimization Glulisin is now clear, namely the final removal of the zinc. ”
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More information:
Richard B. Gillis et al. Analysis of Insulin Glulisine at the Molecular Level by X-ray Crystallography and Biophysical Techniques, Scientific Reports (2021). DOI: 10.1038 / s41598-021-81251-2 Provided by the University of Manchester
Quote: New research could lead to more treatment options for diabetes patients (2021, January 18), which will be available on January 18, 2021 at https://phys.org/news/2021-01-treatment-options-diabetes-patients.html were retrieved
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