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.
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February 15 1996
Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic β-cells
Thomas NILSSON;
Thomas NILSSON
*Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, Karolinska Hospital, S-17176 Stockholm, Sweden
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Vera SCHULTZ;
Vera SCHULTZ
†Diabetes and Metabolism Unit, Evans Department of Medicine, and Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, U.S.A.
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Per-Olof BERGGREN;
Per-Olof BERGGREN
*Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, Karolinska Hospital, S-17176 Stockholm, Sweden
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Barbara E. CORKEY;
Barbara E. CORKEY
†Diabetes and Metabolism Unit, Evans Department of Medicine, and Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, U.S.A.
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TORNHEIM TORNHEIM
TORNHEIM TORNHEIM
‡
†Diabetes and Metabolism Unit, Evans Department of Medicine, and Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, U.S.A.
‡To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
July 24 1995
Revision Received:
October 04 1995
Accepted:
October 10 1995
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 314 (1): 91–94.
Article history
Received:
July 24 1995
Revision Received:
October 04 1995
Accepted:
October 10 1995
Citation
Thomas NILSSON, Vera SCHULTZ, Per-Olof BERGGREN, Barbara E. CORKEY, TORNHEIM TORNHEIM; Temporal patterns of changes in ATP/ADP ratio, glucose 6-phosphate and cytoplasmic free Ca2+ in glucose-stimulated pancreatic β-cells. Biochem J 15 February 1996; 314 (1): 91–94. doi: https://doi.org/10.1042/bj3140091
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