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1 Unite d'Endocrinologie et Metabolisme, University of Louvain Faculty of Medicine, Brussels, B-1200, Belgium
* To whom correspondence should be addressed. E-mail: henquin{at}endo.ucl.ac.be.
In contrast to pancreatic islets, isolated
-cells stimulated by glucose display irregular
and asynchronous increases in cytoplasmic Ca2+ ([Ca2+]i). Here, clusters of 5-30 cells were
prepared from one single mouse islet or from pools of islets, loaded with fura-2 and studied
with a camera-based system. [Ca2+]i oscillations were compared in pairs of clusters by
computing the difference in period and a synchronization index
. During perifusion with
12mM glucose, the clusters exhibited regular [Ca2+] oscillations that were quasi perfectly
synchronized (
period of 1.4 % and index
close to 1.0) between cells of each cluster. In
contrast, separate clusters were not synchronized even when prepared from one single islet.
Pairs of clusters neighbouring on the same coverslip were not better synchronized than pairs
of clusters examined separately (distinct coverslips). We next attempted to synchronize
clusters perifused with 12mM glucose by applying external signals. A single pulse of 20mM
glucose, 10mM amino acids or 10µM tolbutamide transiently altered [Ca2+]i oscillations but
did not reset the clusters to oscillate synchronously. On a background of 12mM glucose,
repetitive applications (1min/5min) of 10µM tolbutamide but not of 20mM glucose
synchronized separate clusters. Our results identify a level of
-cell heterogeneity
intermediate between single
-cells and the whole islet. They do not support the idea that
substances released by islet cells serve as paracrine synchronizers. However, synchronization
can be achieved by an external signal, if this signal has a sufficient strength to overwhelm the
intrinsic rhythm of glucose-induced oscillations and is repetitively applied.
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