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J Biol Chem, Vol. 275, Issue 9, 6642-6650, March 3, 2000
From the Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Micron-sized sensors were used to monitor glucose
and oxygen levels in the extracellular space of single islets of
Langerhans in real-time. At 10 mM glucose,
oscillations in intraislet glucose concentration were readily detected.
Changes in glucose level correspond to changes in glucose consumption
by glycolysis balanced by mass transport into the islet. Oscillations
had a period of 3.1 ± 0.2 min and amplitude of 0.8 ± 0.1 mM glucose (n = 21). Superimposed on these
oscillations were faster fluctuations in glucose level during the
periods of low glucose consumption. Oxygen level oscillations that were
out of phase with the glucose oscillations were also detected.
Oscillations in both oxygen and glucose consumption were strongly
dependent upon extracellular Ca2+ and sensitive to
nifedipine. Simultaneous measurements of glucose with intracellular
Ca2+ ([Ca2+]i) revealed that
decreases in [Ca2+]i preceded increases in
glucose consumption by 7.4 ± 2.1 s during an oscillation
(n = 9). Conversely, increases in [Ca2+]i preceded increases in oxygen consumption
by 1.5 ± 0.2 s (n = 4). These results
suggest that during oscillations, bursts of glycolysis begin after
Ca2+ has stopped entering the cell. Glycolysis stimulates
further Ca2+ entry, which in turn stimulates increases in
respiration. The data during oscillation are in contrast to the time
course of events during initial exposure to glucose. Under these
conditions, a burst of oxygen consumption precedes the initial rise in
[Ca2+]i. A model to explain these results is described.
Correlated Oscillations in Glucose Consumption, Oxygen
Consumption, and Intracellular Free Ca2+ in Single
Islets of Langerhans*
*
This work was supported by National Institutes of Health
Grant RO1-DK46960.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 352-392-9839;
Fax: 352-392-4582; E-mail: rtkenn@chem.ufl.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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