Insulin fibrillation: toward strategies for attenuating the process

Area of Science:

• Biochemistry and pharmaceutical sciences.
• Protein aggregation and stabilization.

Background:

• The therapeutic discovery of insulin revolutionized diabetes care.
• Insulin's therapeutic utility is limited by its propensity for rapid, irreversible aggregation and fibrillation.
• Despite extensive research over 50 years, effective strategies to prevent insulin fibrillation remain elusive.

Purpose of the Study:

• To provide a comprehensive overview of chemical, physical, and biological approaches to attenuate and inhibit insulin aggregation and fibrillation.
• To analyze the efficacy of various strategies in modulating insulin fibrillation.

Main Methods:

• Review of chemical, physical, and biological studies on insulin fibrillation.
• Detailed characterization of the insulin fibrillation process.
• Focus on inhibition and modulation using nanoparticles, proteins/peptides, and cyclic/non-cyclic compounds.

Main Results:

• Various organic compounds, nanoparticles, and protein/peptide inhibitors have been investigated to combat insulin aggregation.
• Physicochemical laws govern insulin aggregation, necessitating multifaceted inhibition strategies.
• Different approaches show potential in attenuating or inhibiting insulin fibrillation.

Conclusions:

• Understanding the physicochemical basis of insulin fibrillation is crucial.
• Nanoparticles, proteins/peptides, and small molecules offer promising avenues for inhibiting insulin aggregation.
• Further research can enhance the stability of pharmaceutical proteins and peptides, improving therapeutic outcomes.