Glucose-induced metabolic oscillations parallel those of Ca2+ and insulin release in clonal insulin-secreting cells -: A multiwell approach to oscillatory cell behavior

Insulin secretion from glucose-stimulated pancreatic beta -cells is oscillatory, and this is thought to result from oscillations in glucose metabolism. One of the primary metabolic stimulus-secretion coupling factors is the ATP/ADP ratio, which can oscillate as a result of oscillations in glycolysis. Using a novel multiwell culture plate system, we examined oscillations in insulin release and the ATP/ADP ratio in the clonal insulin-secreting cell lines HIT T-15 and INS-1. Insulin secretion from HIT cells grown in multiwell plates oscillated with a period of 4 min, similar to that seen previously in perifusion experiments. Oscillations in the ATP/ADP ratio in cells grown under the same conditions also occurred with a period of 4 min, as did oscillations in [Ca2+](i) monitored by fluorescence microscopy. In INS-1 cells oscillations in insulin secretion, the ATP/ADP ratio, and [Ca2+](i) were also seen, but with a shorter period of about 1.5 min. These observations of oscillations in the ATP/ADP ratio are consistent with their proposed role in driving the oscillations in [Ca2+](i) and insulin secretion. Furthermore, these data show that, at least in the clonal beta -cell lines, cell contact or even circulatory connection is not necessary for synchronous oscillations induced by a rise in glucose.