Dihydroxyacetone-induced Oscillations in Cytoplasmic Free Ca2+ and the ATP/ADP Ratio in Pancreatic β-Cells at Substimulatory Glucose

Lisa Juntti-Berggren, Dominic Luc Webb, Per O.G. Arkhammar, Vera Schultz, Elke K.H. Schweda, Keith Tornheim, Per Olof Berggren

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Glucose stimulation of pancreatic β-cells causes oscillatory influx of Ca2+, leading to pulsatile insulin secretion. We have proposed that this is due to oscillations of glycolysis and the ATP/ADP ratio, which modulate the activity of ATP-sensitive K+ channels. We show here that dihydroxyacetone, a secretagogue that feeds into glycolysis below the putative oscillator phosphofructokinase, could cause a single initial peak in cytoplasmic free Ca2+ ([Ca2+]i) but did not by itself cause repeated oscillations in [Ca2+]i in mouse pancreatic β-cells. However, in the presence of a substimulatory concentration of glucose (4 mM), dihydroxyacetone induced [Ca 2+-]i oscillations. Furthermore, these oscillations correlated with oscillations in the ATP/ADP ratio, as seen previously with glucose stimulation. Insulin secretion in response to dihydroxyacetone was transient in the absence of glucose but was considerably enhanced and somewhat prolonged in the presence of a substimulatory concentration of glucose, in accordance with the enhanced [Ca2+]i response. These results are consistent with the hypothesized role of phosphofructokinase as the generator of the oscillations. Dihydroxyacetone may affect phosphofructokinase by raising the free concentration of fructose 1,6-bisphosphate to a critical level at which it activates the enzyme autocatalytically, thereby inducing the pulses of phosphofructokinase activity that cause the metabolic oscillations.

Original languageEnglish (US)
Pages (from-to)40710-40716
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number42
DOIs
StatePublished - Oct 17 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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