Insulin fibrillation: toward strategies for attenuating the process

Dark days for diabetic patients were transformed into an era of hope when the therapeutic usage of insulin was discovered. However, those initial glory days changed to being somewhat gloomy, when it was discovered that insulin easily undergoes undesirable, fast, and non-reversible aggregation and fibrillation. After more than half a century of intensive attempts to limit the rate of the insulin aggregation and fibrillation, there is no clear-cut strategy for eliminating these processes once and for all. A plethora of studies focused on using various organic compounds to combat the process, whereas other researchers believe that the process can be inhibited (or altered) by well-designed nanoparticles. In an attempt to inhibit insulin aggregation, some other approaches, such as protein/peptide inhibitors, have been considered for therapeutic purposes. Beyond biological processes and interactions between biological molecules, there are also strong physicochemical laws. Therefore, the goal of this article is to provide an overview of chemical, physical, and biological studies dedicated to the analysis of approaches that attenuate and inhibit insulin aggregation and fibrillation. After a detailed characterization of the insulin fibrillation process, this review focuses on various aspects related to the inhibition and modulation of insulin fibrillation using nanoparticles, proteins/peptides, and cyclic and non-cyclic compounds. Hopefully, these findings will pave the way for scientists in various fields to increase the stability of pharmaceutical proteins and peptides.