Amino acid compound 2 (AAC2)–human insulin (hINS) nanofiber–receptor complex (AAC2-hINS complex)

The Amino acid compound 2 (AAC2)–human insulin (hINS) nanofiber–receptor complex is a supramolecular therapeutic assembly designed to address the limitations of conventional insulin therapy in diabetes and neurodegenerative diseases [1, 2]. AAC2 is a self-assembling lysine dipeptide modified with a coumarin moiety that forms positively charged nanofibers, which electrostatically bind negatively charged insulin to create a stable complex [1, 3]. This assembly functions as a dual-target system, interacting with both the insulin receptor (IR) and the leptin receptor (LepR) [1, 2]. AAC2 acts as an atypical ligand for LepR, activating the LepR/PKCζ/GLUT1 signaling pathway to enhance glucose uptake in insulin-insensitive tissues like the blood-brain barrier, while the bound insulin targets the canonical IR/PI3K/Akt pathway for GLUT4-mediated glucose disposal [1, 2]. This combinatorial approach improves systemic glycemic control, extends the therapeutic window of insulin, and reduces the risk of hypoglycemia [1]. Furthermore, the complex has demonstrated neuroprotective properties by regulating synaptic gene expression and preserving brain composition in models of Alzheimer's disease [2, 3].

Other names

AAC2-hINS supramolecular complexAmino acid compound 2-insulin nanofiberAAC2-insulin assemblyAAC2-hINS complex

Dual activation of the leptin receptor (LepR) via an atypical binding site and the insulin receptor (IR), facilitating both GLUT1- and GLUT4-mediated glucose uptake and stabilizing insulin signaling.