biostudies-literatureLee ANational Institute of Allergy and Infectious DiseasesNational Institute of Allergy and Infectious Diseases (NIAID)NIAID NIH HHSRalph and Marian Falk Medical Research Catalyst AwardNational Science Foundation85https://www.ebi.ac.uk/biostudies/studies/S-EPMC12853802biostudies-literatureUnknown24(1)Therapies for type 2 diabetes primarily target hyperglycemia; however, complications are also triggered by advanced glycation end products (AGEs). We hypothesize that the anti-diabetic efficacy of insulin-like growth factor-binding protein 4 (IGFBP4) is enhanced when it assembles with a specific amino acid compound-2 (AAC2) into nanostructures. Their effects were examined in vitro and in ob/ob mice treated for 30 days with the AAC2-IGFBP4 complex or its individual components. IGFBP4-mediated glucose uptake in human and mouse preadipocytes was enhanced by complex formation with AAC2. This complex was confirmed by Fourier-transform mid-infrared spectroscopy, electrophoresis, and AFM. In ob/ob mice, the complex prolonged IGFBP4 circulation and amplified the effects of the individual componentJournal of nanobiotechnologyBidirectional regulation of liver sinusoidal clearance by amino acid nanofibers and IGFBP4 complex: effects on HbA1c.PMC12853802AI170880R56 AI170880CHE-2106924Castelli SLYu LNoria SFOrtiz MKowdley DNeedleman BJRodriguez-Saona LLee ASellers PParquette JRPokharel BLeung JHTaneja SGanesan LPZiouzenkova OfalseBidirectional regulation of liver sinusoidal clearance by amino acid nanofibers and IGFBP4 complex: effects on HbA1c.Therapies for type 2 diabetes primarily target hyperglycemia; however, complications are also triggered by advanced glycation end products (AGEs). We hypothesize that the anti-diabetic efficacy of insulin-like growth factor-binding protein 4 (IGFBP4) is enhanced when it assembles with a specific amino acid compound-2 (AAC2) into nanostructures. Their effects were examined in vitro and in ob/ob mice treated for 30 days with the AAC2-IGFBP4 complex or its individual components. IGFBP4-mediated glucose uptake in human and mouse preadipocytes was enhanced by complex formation with AAC2. This complex was confirmed by Fourier-transform mid-infrared spectroscopy, electrophoresis, and AFM. In ob/ob mice, the complex prolonged IGFBP4 circulation and amplified the effects of the individual component2025-01-01T00:00:00Z2025 Dec2026-06-16T07:09:53.101Z2026-06-16T03:09:56.157ZS-EPMC128538024145438710.1186/s12951-025-03943-5