Scientists found that the natural human peptide LL‑37 can stick to the hormone IAPP, which normally clumps together in the pancreas and harms insulin‑producing cells in type‑2 diabetes. In lab tests, LL‑37 stopped these clumps from forming and protected the cells, suggesting it might help guard against diabetes‑related damage.

Amyloid self-assembly of islet amyloid polypeptide (IAPP) is linked to pancreatic inflammation, β-cell degeneration, and the pathogenesis of type 2 diabetes (T2D). The multifunctional host-defence peptides (HDPs) cathelicidins play crucial roles in inflammation. Here, we show that the antimicrobial and immunomodulatory polypeptide human cathelicidin LL-37 binds IAPP with nanomolar affinity and effectively suppresses its amyloid self-assembly and related pancreatic β-cell damage in vitro. In addition, we identify key LL-37 segments that mediate its interaction with IAPP. Our results suggest a possible protective role for LL-37 in T2D pathogenesis and offer a molecular basis for the design of LL-37-derived peptides that combine antimicrobial, immunomodulatory, and T2D-related anti-amyloid functions as promising candidates for multifunctional drugs.