Regulation mechanism of human insulin fibrillation by l-lysine carbon dots: low concentration accelerates but high concentration inhibits the fibrillation process

Abstract

The fibrillation process of human insulin (HI) is closely related to the therapy for type II diabetes (T2D). Due to changes in the spatial structure of HI, the fibrillation process of HI takes place in the body, which leads to a significant decrease in normal insulin levels. L-Lysine CDs with a size of around 5 nm were synthesized and used to adjust and control the fibrillation process of HI. ThT fluorescence analysis and transmission electron microscopy (TEM) characterization of the CDs showed the role of HI fibrillation from the perspective of the kinetics of HI fibrillation and regulation. Isothermal titration calorimetry (ITC) was used to explore the regulatory mechanism of CDs at all stages of HI fibrillation from the perspective of thermodynamics. Contrary to common sense, when the concentration of CDs is less than 1/50 of the HI, CDs will promote the growth of fibres, while a high concentration of CDs will inhibit the growth of fibres. The experimental results of ITC clearly prove that different concentrations of CDs will correspond to different pathways of the combination between CDs and HI. CDs have a strong ability to combine with HI during the lag time, and the degree of combination has become the main factor influencing the fibrillation process.