The amyloid aggregation of peptides and proteins is a hallmark of neurological disorders and type 2 diabetes.Human islet amyloid polypeptide (lAPP),co-secreted with insulin by pancreatic β-cells,plays dual roles in both glycemic control and the pathology of type 2 diabetes.While lAPP can activate the NLRP3 inflammasome and modulate cellular autophagy,apoptosis and extracellular matrix metabolism,no data is available concing intracellular protein expression upon exposure to the polypeptide.More surprisingly,how intracellular protein expression is modulated by nanoparticle inhibitors of protein aggregation remains entirely unknown.In this study,we first examined the changing proteomes of βTC6,a pancreatic β-cell line,upon exposure to monomeric,oligomeric and fibrillar lAPP,and detailed cellular protein expression rescued by graphene quantum dots (GQDs),an lAPP inhibitor.We found that 29 proteins were significantly dysregulated by the IAPP species,while majority of these proteins were nucleotide-binding proteins.Collectively,our liquid chromatography tandem-mass spectrometry,fluorescence quenching,helium ion microscopy,cytotoxicity and discreet molecular dynamics simulations data revealed a remarkable capacity of GQDs in regulating aberrant protein expression through H-bonding and hydrophobic interactions,pointing to nanomedicine as a new frontier against human amyloid diseases.