Insulin amyloid fibrils (IAF)

Insulin amyloid fibrils are insoluble, highly ordered protein aggregates characterized by a cross-beta sheet quaternary structure, formed through the misfolding and polymerization of insulin molecules. This pathological process is most commonly observed in patients with diabetes mellitus at sites of frequent subcutaneous insulin injections, a condition known as injection-site amyloidosis or "insulin balls." These fibrils are problematic because they sequester active insulin, preventing its absorption into the bloodstream and leading to poor glycemic control and unpredictable blood glucose fluctuations. While insulin is biologically active in its monomeric alpha-helical form, the transition to the amyloid state renders it therapeutically inert and physically obstructive. Current pharmacological interest focuses on the development of stabilizers and inhibitors, such as polyphenols or specific surfactants, to prevent fibril formation during storage and after administration. Understanding the kinetics of insulin aggregation is essential for improving the safety and efficacy of long-term insulin replacement therapy.

Other names

Insulin fibrilsInsulin amyloidInjection-site amyloidosis depositsIatrogenic insulin amyloidInsulin balls

Inhibition of insulin fibrillogenesis by stabilizing the native monomeric or hexameric state, or by disrupting the cross-beta sheet assembly of misfolded insulin molecules.