ABSTRACT Glucose‐stimulated insulin secretion (GSIS) in β cells depends critically on membrane depolarization–induced Ca 2+ 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.
Tsurumoto et al. (Mon,) studied this question.