Dathe M, Gast K, Zirwer D, Welfle H, Mehlis B
Institute of Drug Research, Academy of Sciences of the GDR, Berlin.
Int J Pept Protein Res. 1990 Oct;36(4):344-9. doi: 10.1111/j.1399-3011.1990.tb01292.x.
The process of insulin aggregation in neutral solutions was studied by dynamic light scattering. Solutions of different concentrations were subjected to thermal and mechanical stress (37 degrees, rotation) for a period of 4 weeks. The starting solutions contained exclusively one particle distribution of insulin in the association equilibrium with hexamers as the largest structures. After a lag period of about 8 days the solutions showed continuously increasing scattering intensities but did not evolve perceptible turbidity within the experimental period. A more rapid increase in scattering intensity was observed in diluted than in concentrated solutions. The analysis of scattering data unexpectedly revealed that insulin species did not grow continuously. After the lag period one additional relatively restricted size distribution with particles of a mean radius of about 100 nm was found, the amount of which increased continuously with time. The occurrence of these particles seems to be related to adsorption phenomena of insulin to the solid interface. We assume the 100 nm-class of aggregates to be a transient state in the physical destabilization process of insulin solutions.
通过动态光散射研究了胰岛素在中性溶液中的聚集过程。将不同浓度的溶液在37摄氏度下进行热应激和机械应激（旋转），持续4周。起始溶液仅包含胰岛素的一种颗粒分布，在缔合平衡中，六聚体是最大的结构。经过约8天的延迟期后，溶液的散射强度持续增加，但在实验期内未出现明显的浑浊。稀释溶液中观察到的散射强度增加比浓缩溶液中更快。散射数据分析意外地发现，胰岛素种类并非持续生长。延迟期后，发现了另一种相对受限的尺寸分布，其颗粒平均半径约为100纳米，其数量随时间持续增加。这些颗粒的出现似乎与胰岛素在固体界面的吸附现象有关。我们认为100纳米级的聚集体是胰岛素溶液物理不稳定过程中的一个过渡状态。
