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

Jude T. Deeney, Martin Köhler, Kari Kubik, Graham Brown, Vera Schultz, Keith Tornheim, Barbara E. Corkey, Per Olof Berggren

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Insulin secretion from glucose-stimulated pancreatic β-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 β-cell lines, cell contact or even circulatory connection is not necessary for synchronous oscillations induced by a rise in glucose.

Original languageEnglish (US)
Pages (from-to)36946-36950
Number of pages5
JournalJournal of Biological Chemistry
Volume276
Issue number40
DOIs
StatePublished - Oct 5 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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