Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic β-cells

Thomas Nilsson, Vera Schultz, Per Olof Berggren, Barbara E. Corkey, Keith Tornheim

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Closure of ATP-sensitive K+ (KATP) channels is part of the stimulus-secretion coupling mechanism in the pancreatic β-cell, leading to membrane depolarization and influx of Ca2+ through voltage-sensitive L-type Ca2+ channels. The elevated ATP/ADP ratio seen in the presence of high levels of glucose has been postulated to mediate the glucose-induced closure of the KATP channels and rise in cytoplasmic free Ca2+ concentration ([Ca2+]i), or alternatively to be a consequence of activation of mitochondrial dehydrogenases by the increase in [Ca2+]i. To distinguish between these two possibilities, the time course of the change in the ATP/ADP ratio was determined in comparison with that of [Ca2+]i. We here show that a severalfold rise in the ATP/ADP ratio occurs rapidly on stimulation of suspensions of mouse pancreatic β-cells with glucose. The change in the ATP/ ADP ratio is an early event that begins within 20-40 s and precedes the rise in [Ca2+]i. The temporal relationship indicates that the adenine nucleotide changes cannot be a consequence of the [Ca2+]i changes and may indeed be the connecting link between glucose metabolism and [Ca2+]i changes. When the cells were sequentially treated with high glucose concentration, clonidine and finally high extracellular Ca2+ concentration to induce synchronized oscillations in [Ca2+]i in the cell suspension, corresponding oscillations in the ATP/ADP ratio were observed. Glucose 6-phosphate levels oscillated out of phase with the ATP/ADP ratio. These results support the hypothesis that the Ca2+ oscillations previously observed in glucose-stimulated single islets or β-cells may reflect oscillations in the ATP/ADP ratio that accompany oscillatory glycolysis.

Original languageEnglish
Pages (from-to)91-94
Number of pages4
JournalBiochemical Journal
Volume314
Issue number1
StatePublished - Feb 15 1996
Externally publishedYes

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Adenosine Diphosphate Glucose
Glucose-6-Phosphate
Adenosine Diphosphate
Adenosine Triphosphate
Glucose
KATP Channels
Suspensions
Adenine Nucleotides
Depolarization
Clonidine
Glycolysis
Islets of Langerhans
Metabolism
Oxidoreductases
Chemical activation
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic β-cells. / Nilsson, Thomas; Schultz, Vera; Berggren, Per Olof; Corkey, Barbara E.; Tornheim, Keith.

In: Biochemical Journal, Vol. 314, No. 1, 15.02.1996, p. 91-94.

Research output: Contribution to journalArticle

Nilsson, T, Schultz, V, Berggren, PO, Corkey, BE & Tornheim, K 1996, 'Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic β-cells', Biochemical Journal, vol. 314, no. 1, pp. 91-94.
Nilsson, Thomas ; Schultz, Vera ; Berggren, Per Olof ; Corkey, Barbara E. ; Tornheim, Keith. / Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic β-cells. In: Biochemical Journal. 1996 ; Vol. 314, No. 1. pp. 91-94.
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