Glucose-stimulated increase in cytoplasmic pH precedes increase in free Ca2+ in pancreatic β-cells: A possible role for pyruvate

Lisa Juntti-Berggren, Vildan N. Civelek, Per Olof Berggren, Vera Schultz, Barbara E. Corkey, Keith Tornheim

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The temporal relationship of glucose-induced increases in cytoplasmic pH (pHi) and cytoplasmic free Ca2+ was studied in single mouse pancreatic β-cells and suspensions of clonal β-cells (HIT). In both preparations of cells the increase in pHi preceded the cytoplasmic free Ca2+ increase. Therefore the alkalinization cannot be a consequence of the Ca2+ influx. A potential metabolic mechanism for the increase in pHi; involving stimulation of pyruvate transport and oxidation, was demonstrated in a model system of liver mitochondria incubated with pyruvate, ATP, and hexokinase to which glucose was then added to initiate ATP use. The involvement of this mechanism in β-cells is suggested by the observation that the alkalinization was prevented in most cells by incubation with 3-hydroxycyanocinnamate, a mitochondrial pyruvate transport inhibitor. On the other hand, the inhibited cells exhibited normal Ca2+ responses to glucose stimulation. This indicates that neither pyruvate metabolism nor the alkalinization is of critical importance for the Ca2+ signal, though pyruvate oxidation or its metabolites may be important in downstream regulation of secretion.

Original languageEnglish
Pages (from-to)14391-14395
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number20
StatePublished - May 20 1994
Externally publishedYes

Fingerprint

Glucagon-Secreting Cells
Pyruvic Acid
Glucose
Adenosine Triphosphate
Oxidation
Mitochondria
Hexokinase
Metabolites
Metabolism
Liver Mitochondrion
Liver
Suspensions

ASJC Scopus subject areas

  • Biochemistry

Cite this

Juntti-Berggren, L., Civelek, V. N., Berggren, P. O., Schultz, V., Corkey, B. E., & Tornheim, K. (1994). Glucose-stimulated increase in cytoplasmic pH precedes increase in free Ca2+ in pancreatic β-cells: A possible role for pyruvate. Journal of Biological Chemistry, 269(20), 14391-14395.

Glucose-stimulated increase in cytoplasmic pH precedes increase in free Ca2+ in pancreatic β-cells : A possible role for pyruvate. / Juntti-Berggren, Lisa; Civelek, Vildan N.; Berggren, Per Olof; Schultz, Vera; Corkey, Barbara E.; Tornheim, Keith.

In: Journal of Biological Chemistry, Vol. 269, No. 20, 20.05.1994, p. 14391-14395.

Research output: Contribution to journalArticle

Juntti-Berggren, L, Civelek, VN, Berggren, PO, Schultz, V, Corkey, BE & Tornheim, K 1994, 'Glucose-stimulated increase in cytoplasmic pH precedes increase in free Ca2+ in pancreatic β-cells: A possible role for pyruvate', Journal of Biological Chemistry, vol. 269, no. 20, pp. 14391-14395.
Juntti-Berggren L, Civelek VN, Berggren PO, Schultz V, Corkey BE, Tornheim K. Glucose-stimulated increase in cytoplasmic pH precedes increase in free Ca2+ in pancreatic β-cells: A possible role for pyruvate. Journal of Biological Chemistry. 1994 May 20;269(20):14391-14395.
Juntti-Berggren, Lisa ; Civelek, Vildan N. ; Berggren, Per Olof ; Schultz, Vera ; Corkey, Barbara E. ; Tornheim, Keith. / Glucose-stimulated increase in cytoplasmic pH precedes increase in free Ca2+ in pancreatic β-cells : A possible role for pyruvate. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 20. pp. 14391-14395.
@article{9616816da09b43649ae882a6bb0f2b19,
title = "Glucose-stimulated increase in cytoplasmic pH precedes increase in free Ca2+ in pancreatic β-cells: A possible role for pyruvate",
abstract = "The temporal relationship of glucose-induced increases in cytoplasmic pH (pHi) and cytoplasmic free Ca2+ was studied in single mouse pancreatic β-cells and suspensions of clonal β-cells (HIT). In both preparations of cells the increase in pHi preceded the cytoplasmic free Ca2+ increase. Therefore the alkalinization cannot be a consequence of the Ca2+ influx. A potential metabolic mechanism for the increase in pHi; involving stimulation of pyruvate transport and oxidation, was demonstrated in a model system of liver mitochondria incubated with pyruvate, ATP, and hexokinase to which glucose was then added to initiate ATP use. The involvement of this mechanism in β-cells is suggested by the observation that the alkalinization was prevented in most cells by incubation with 3-hydroxycyanocinnamate, a mitochondrial pyruvate transport inhibitor. On the other hand, the inhibited cells exhibited normal Ca2+ responses to glucose stimulation. This indicates that neither pyruvate metabolism nor the alkalinization is of critical importance for the Ca2+ signal, though pyruvate oxidation or its metabolites may be important in downstream regulation of secretion.",
author = "Lisa Juntti-Berggren and Civelek, {Vildan N.} and Berggren, {Per Olof} and Vera Schultz and Corkey, {Barbara E.} and Keith Tornheim",
year = "1994",
month = "5",
day = "20",
language = "English",
volume = "269",
pages = "14391--14395",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "20",

}

TY - JOUR

T1 - Glucose-stimulated increase in cytoplasmic pH precedes increase in free Ca2+ in pancreatic β-cells

T2 - A possible role for pyruvate

AU - Juntti-Berggren, Lisa

AU - Civelek, Vildan N.

AU - Berggren, Per Olof

AU - Schultz, Vera

AU - Corkey, Barbara E.

AU - Tornheim, Keith

PY - 1994/5/20

Y1 - 1994/5/20

N2 - The temporal relationship of glucose-induced increases in cytoplasmic pH (pHi) and cytoplasmic free Ca2+ was studied in single mouse pancreatic β-cells and suspensions of clonal β-cells (HIT). In both preparations of cells the increase in pHi preceded the cytoplasmic free Ca2+ increase. Therefore the alkalinization cannot be a consequence of the Ca2+ influx. A potential metabolic mechanism for the increase in pHi; involving stimulation of pyruvate transport and oxidation, was demonstrated in a model system of liver mitochondria incubated with pyruvate, ATP, and hexokinase to which glucose was then added to initiate ATP use. The involvement of this mechanism in β-cells is suggested by the observation that the alkalinization was prevented in most cells by incubation with 3-hydroxycyanocinnamate, a mitochondrial pyruvate transport inhibitor. On the other hand, the inhibited cells exhibited normal Ca2+ responses to glucose stimulation. This indicates that neither pyruvate metabolism nor the alkalinization is of critical importance for the Ca2+ signal, though pyruvate oxidation or its metabolites may be important in downstream regulation of secretion.

AB - The temporal relationship of glucose-induced increases in cytoplasmic pH (pHi) and cytoplasmic free Ca2+ was studied in single mouse pancreatic β-cells and suspensions of clonal β-cells (HIT). In both preparations of cells the increase in pHi preceded the cytoplasmic free Ca2+ increase. Therefore the alkalinization cannot be a consequence of the Ca2+ influx. A potential metabolic mechanism for the increase in pHi; involving stimulation of pyruvate transport and oxidation, was demonstrated in a model system of liver mitochondria incubated with pyruvate, ATP, and hexokinase to which glucose was then added to initiate ATP use. The involvement of this mechanism in β-cells is suggested by the observation that the alkalinization was prevented in most cells by incubation with 3-hydroxycyanocinnamate, a mitochondrial pyruvate transport inhibitor. On the other hand, the inhibited cells exhibited normal Ca2+ responses to glucose stimulation. This indicates that neither pyruvate metabolism nor the alkalinization is of critical importance for the Ca2+ signal, though pyruvate oxidation or its metabolites may be important in downstream regulation of secretion.

UR - http://www.scopus.com/inward/record.url?scp=0028334658&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028334658&partnerID=8YFLogxK

M3 - Article

C2 - 8182044

AN - SCOPUS:0028334658

VL - 269

SP - 14391

EP - 14395

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 20

ER -