Human islet amyloid polypeptide (hIAPP) protofibril (hIAPP protofibril)

Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-amino acid peptide hormone co-secreted with insulin by pancreatic beta-cells (UniProt P10997). In its monomeric form, hIAPP contributes to glucose homeostasis by slowing gastric emptying and promoting satiety. However, in type 2 diabetes mellitus (T2DM), hIAPP undergoes a conformational change, aggregating into toxic oligomers and protofibrils that eventually form mature amyloid deposits (PubMed: 30612031). These protofibrils are highly cytotoxic, causing beta-cell membrane disruption, oxidative stress, and apoptosis, which leads to the progressive decline of insulin secretion (PubMed: 29453414). Therapeutic efforts are directed at inhibiting the aggregation process, destabilizing existing protofibrils, or neutralizing their toxic effects to preserve pancreatic function. While several small molecules and antibodies are under investigation, no drugs specifically targeting hIAPP protofibrils are currently FDA-approved (PubMed: 31505263).

Other names

Amylin protofibrilIslet amyloid polypeptide protofibrilhIAPP aggregateDiabetes-associated peptide protofibrilToxic hIAPP oligomer

Inhibition of amyloid aggregation, destabilization of pre-formed protofibrils, and neutralization of toxic oligomeric species to prevent beta-cell membrane disruption and apoptosis (PubMed: 31505263).