Evidence map›Paper›PMID 33462295›Full record

ArticleScientific reports2021

Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques.

Richard B Gillis, Hodaya V Solomon, Lata Govada, Neil J Oldham, Vlad Dinu, Shahwar Imran Jiwani, Philemon Gyasi-Antwi, Frank Coffey, Andy Meal, Paul S Morgan and 4 more

Abstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. New Horizons: Next-Generation Insulin Analogues: Structural Principles and Clinical Goals.The Journal of clinical endocrinology and metabolism · 2022
    Review
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Richard B Gillis *Faculty of Medicine and Health Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2HA, UK. richard.gillis@nottingham.ac.uk.
Hodaya V Solomon *Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, London, SW7 2AZ, UK.
Lata GovadaDivision of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, London, SW7 2AZ, UK.
Neil J OldhamSchool of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Vlad DinuNational Centre for Macromolecular Hydrodynamics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
Shahwar Imran JiwaniFaculty of Medicine and Health Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2HA, UK.
Philemon Gyasi-AntwiFaculty of Medicine and Health Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2HA, UK.
Frank CoffeyFaculty of Medicine and Health Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2HA, UK.
Andy MealFaculty of Medicine and Health Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2HA, UK.
Paul S MorganFaculty of Medicine and Health Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2HA, UK.
Stephen E HardingNational Centre for Macromolecular Hydrodynamics, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
John R HelliwellDepartment of Chemistry, University of Manchester, Manchester, M13 9PL, UK.
Naomi E ChayenDivision of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, London, SW7 2AZ, UK. n.chayen@imperial.ac.uk.
Gary G AdamsFaculty of Medicine and Health Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2HA, UK. gary.adams@nottingham.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study concerns glulisine, a rapid-acting insulin analogue that plays a fundamental role in diabetes management. We have applied a combination of methods namely X-ray crystallography, and biophysical characterisation to provide a detailed insight into the structure and function of glulisine. X-ray data provided structural information to a resolution of 1.26 Å. Crystals belonged to the H3 space group with hexagonal (centred trigonal) cell dimensions a = b = 82.44 and c = 33.65 Å with two molecules in the asymmetric unit. A unique position of D21Glu, not present in other fast-acting analogues, pointing inwards rather than to the outside surface was observed. This reduces interactions with neighbouring molecules thereby increasing preference of the dimer form. Sedimentation velocity/equilibrium studies revealed a trinary system of dimers and hexamers/dihexamers in dynamic equilibrium. This new information may lead to better understanding of the pharmacokinetic and pharmacodynamic behaviour of glulisine which might aid in improving formulation regarding its fast-acting role and reducing side effects of this drug.

Indexed as

Biophysical PhenomenaCrystallography, X-RayHumansHypoglycemic AgentsInsulinProtein MultimerizationProtein Structural ElementsStructure-Activity RelationshipHypoglycemic AgentsInsulininsulin glulisine

Identifiers

PMID33462295
PMCPMC7814034

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.