Although bulk endocytosis has been found in a number of neuronal and endocrine cells,the molecular mechanism and physiological function of bulk endocytosis remain elusive.In pancreatic beta cells,we have observed bulk-like endocytosis evoked both by flash photolysis and trains of depolarization.Bulk-like endocytosis is a clathrin-independent process that is facilitated by enhanced extracellular Ca2+ entry and suppressed by the inhibition of dynamin function.Moreover,defects in bulklike endocytosis are accompanied by hyperinsulinemia in primary beta cells dissociated from diabetic KKAy mice,which suggests that bulk-like endocytosis plays an important role in maintaining the exo-endocytosis balance and beta cell secretory capability.