Vesicle fusion mechanisms mediated by synaptosomal-associated protein 25 and its role in insulin secretion defects in type 2 diabetes mellitus

The occurrence and development of type 2 diabetes mellitus (T2DM) are closely associated with defects in insulin secretion. Synaptosomal-associated protein 25 (SNAP25), as a core component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, directly mediates the fusion of insulin secretion granules with the cell membrane and regulates the dynamic balance of insulin secretion stimulated by glucose. The expression defect of SNAP25 in patients with T2DM and model animals directly leads to vesicle fusion disorder, constituting the core pathological link of insulin secretion disorder and exacerbating the deterioration of β-cell function. SNAP25 may serve as a key hub for multi-target synergistic intervention, and its genetic polymorphism and the plasticity of its regulatory network offer novel strategies for precision therapy. This article innovatively integrated multidimensional regulatory mechanisms, including calcium channel activity, G-protein-coupled signaling and epigenetic modifications, to systematically analyze the spatiotemporal-specific regulatory network of SNAP25 in insulin secretion, providing a theoretical basis for T2DM therapeutic strategies targeting vesicle fusion.