The University of Nottingham, Faculty of Medicine and Health Sciences, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
The University of Nottingham, School of Biosciences, National Centre for Macromolecular Hydrodynamics (NCMH), Sutton Bonington Campus, Sutton Bonington, Leicestershire, LE12 5RD, UK.
Sci Rep. 2017 Aug 4;7(1):7287. doi: 10.1038/s41598-017-06642-w.
Single, double and triple doses of the synthetic insulins glargine and degludec currently used in patient therapy are characterised using macromolecular hydrodynamic techniques (dynamic light scattering and analytical ultracentrifugation) in an attempt to provide the basis for improved personalised insulin profiling in patients with diabetes. Using dynamic light scattering and sedimentation velocity in the analytical ultracentrifuge glargine was shown to be primarily dimeric under solvent conditions used in current formulations whereas degludec behaved as a dihexamer with evidence of further association of the hexamers ("multi-hexamerisation"). Further analysis by sedimentation equilibrium showed that degludec exhibited reversible interaction between mono- and-di-hexamer forms. Unlike glargine, degludec showed strong thermodynamic non-ideality, but this was suppressed by the addition of salt. With such large injectable doses of synthetic insulins remaining in the physiological system for extended periods of time, in some case 24-40 hours, double and triple dose insulins may impact adversely on personalised insulin profiling in patients with diabetes.
目前用于患者治疗的甘精胰岛素和德谷胰岛素的单、双、三倍剂量，使用高分子流体力学技术（动态光散射和分析超速离心）进行了表征，以期为糖尿病患者的个体化胰岛素分析提供基础。使用分析超速离心的动态光散射，在当前配方中使用的溶剂条件下，甘精胰岛素主要表现为二聚体，而德谷胰岛素表现为二六聚体，并且存在六聚体的进一步缔合（“多六聚体化”）。进一步的沉降平衡分析表明，德谷胰岛素表现出单六聚体形式和双六聚体形式之间的可逆相互作用。与甘精胰岛素不同，德谷胰岛素表现出强烈的热力学非理想性，但添加盐可以抑制这种非理想性。由于这些大剂量的合成胰岛素在生理系统中长时间（某些情况下为 24-40 小时）保持存在，双剂量和三剂量胰岛素可能会对糖尿病患者的个体化胰岛素分析产生不利影响。
