As an alternative to manual assays that track insulin secretion, we tested a silicon-based biosensor that allows automated monitoring of extracellular acidification. Glucose stimulation of INS-1 and HIT-T15 cells resulted in a rapid increase in extracellular acidification in a biphasic and concentration-dependent fashion much like insulin secretion (EC50 INS-1 = 5 mM and HIT-T15 = 1 mM). This response was attenuated by verapamil (10 muM) and stimulated by administration of glybenclamide (100 nM) or KCl-induced (40 mM) depolarization. These experiments suggest that automated monitoring Of extracellular pH may be a useful assay and support the relevance of linking metabolic activity to insulin secretion. (C) 2002 Elsevier Science (USA). All rights reserved.