Abstract
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 [Ca(2+)](i) monitored by fluorescence microscopy. In INS-1 cells oscillations in insulin secretion, the ATP/ADP ratio, and [Ca(2+)](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 [Ca(2+)](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.
Highlights
Insulin secretion from glucose-stimulated pancreatic -cells is oscillatory, and this is thought to result from oscillations in glucose metabolism
Using the KATP channel-independent pathway to stimulate secretion, investigators found that formycin A, an adenosine analogue which was converted to formycin A-triphosphate in islets, was capable of potentiating insulin secretion independent of glucose concentration (21)
We previously showed that HIT-T15 clonal insulin-secreting cells exhibit large oscillations in insulin secretion with a period of 15–20 min, the peaks of which were superimposed with smaller oscillations of 5– 8 min period, when perifused in a column (3)
Summary
Using the KATP channel-independent pathway to stimulate secretion, investigators found that formycin A, an adenosine analogue which was converted to formycin A-triphosphate in islets, was capable of potentiating insulin secretion independent of glucose concentration (21) These data suggest that ATP or the ATP/ADP ratio is an important metabolic coupling factor that may regulate insulin release independent of [Ca2ϩ]i. Oscillations in insulin release were observed from INS-1 cells attached to multiwell plates These oscillations in insulin release correlated with oscillations in the ATP/ADP ratio and are similar in period to those in [Ca2ϩ]i, confirming a role for metabolic oscillations in oscillatory insulin release
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