Characterization of extracellular and membrane potentials in imeglimin-treated islets

Glucose-stimulated insulin secretion (GSIS) in β cells depends critically on membrane depolarization-induced Ca²⁺ influx. Accordingly, the electrophysiological assessment of intact islets, where β cells act as functional syncytia, is essential for evaluating insulin secretory dynamics. Imeglimin, an oral agent used in treating type 2 diabetes, increases insulin secretion; however, its effects on β-cell electroactivity remain unclear. Here, we investigated extracellular and membrane potentials in imeglimin-treated mouse islets using microelectrode array (MEA) recordings and a plasma membrane potential indicator (PMPI). Imeglimin augmented first-phase insulin release and significantly increased the fraction of the plateau phase (FOPP), an MEA-derived parameter reflecting secretory competence, under 11.1 mM glucose. Consistent with these findings, the increase in PMPI fluorescence demonstrated enhanced membrane depolarization in response to imeglimin at high-glucose concentrations. These findings indicate that imeglimin potentiates β-cell electroactivity, thereby facilitating GSIS at the islet level.