Trifluoperazine, an inhibitor of calcium-calmodulin functions, was used in an attempt to understand the involvement of calcium-calmodulin in glucose-stimulated insulin release. Isolated rat pancreatic islets were used after a two-day period of maintenance in tissue culture. 45Ca2+ uptake and insulin release were measured during 5-min incubations. Dynamic insulin release and 45Ca2+ efflux were assessed during perifusion of the islets preloaded with 45Ca2+ during the culture period. Both phases of insulin release in response to 16.7 mM glucose were inhibited by approximately 60% in the presence of 10 μM trifluoperazine when the latter was added 35 min prior to high glucose. Stimulation of 45Ca2+ efflux by glucose was abolished. Glucose-stimulated 45Ca2+ uptake was inhibited by 43%. These results were compared with those of experiments in which depolarizing concentrations of potassium (24 mM) were used. Trifluoperazine inhibited K+-stimulated insulin release and 45Ca2+ uptake to a similar extent as that seen with glucose. Trifluoperazine did not appear to interfere with the inhibitory effect of glucose on 45Ca2+ efflux seen in the absence of extracellular Ca2+. Moreover, in Ca2+ deprived medium (with no possibility for Ca2+ uptake) insulin release in response to glucose + ouabain or in response to veratridine was also inhibited by trifluoperazine. It can be speculated that calmodulin is involved in the process by which glucose and potassium stimulate Ca2+ uptake, i.e., by activation of voltage-dependent Ca2+ channels in the plasma membrane. In addition, it appears that calmodulin is involved in the process by which glucose and veratridine act on stored calcium to raise the cytosolic Ca2+ concentration. Finally, trifluoperazine did not inhibit insulin release mediated by cyclic AMP (3-isobutyl-1-methyl-xanthine). Two conclusions may be drawn from this finding: (1) calmodulin may not be involved in the process of exocytosis per se and (2) cyclic AMP and glucose seem to mobilize stored calcium by different mechanisms.
Skip Nav Destination
Article navigation
Original contribution|
November 01 1981
Sites of Action of Trifluoperazine in the Inhibition of Glucose-Stimulated Insulin Release
Danilo Janjic;
Danilo Janjic
Institut de Biochimie Clinique, University of Geneva
1211 Geneva 4, Switzerland
Department of Physiology, Tufts University School of Medicine
Boston, Massachusetts
Search for other works by this author on:
Claes B Wollheim;
Claes B Wollheim
Institut de Biochimie Clinique, University of Geneva
1211 Geneva 4, Switzerland
Department of Physiology, Tufts University School of Medicine
Boston, Massachusetts
Search for other works by this author on:
Eberhard G Siegel;
Eberhard G Siegel
Institut de Biochimie Clinique, University of Geneva
1211 Geneva 4, Switzerland
Department of Physiology, Tufts University School of Medicine
Boston, Massachusetts
Search for other works by this author on:
Yodphat Krausz;
Yodphat Krausz
Institut de Biochimie Clinique, University of Geneva
1211 Geneva 4, Switzerland
Department of Physiology, Tufts University School of Medicine
Boston, Massachusetts
Search for other works by this author on:
Geoffrey W G Sharp
Geoffrey W G Sharp
Institut de Biochimie Clinique, University of Geneva
1211 Geneva 4, Switzerland
Department of Physiology, Tufts University School of Medicine
Boston, Massachusetts
Search for other works by this author on:
Address reprint requests to Dr. Claes B. Wollheim, Institut de Biochimie Clinique, University of Geneva, Sentier de la Roseraie, 1211 Geneva 4, Switzerland.
Diabetes 1981;30(11):960–966
Article history
Received:
March 18 1981
Revision Received:
July 13 1981
Accepted:
July 13 1981
PubMed:
6170535
Citation
Danilo Janjic, Claes B Wollheim, Eberhard G Siegel, Yodphat Krausz, Geoffrey W G Sharp; Sites of Action of Trifluoperazine in the Inhibition of Glucose-Stimulated Insulin Release. Diabetes 1 November 1981; 30 (11): 960–966. https://doi.org/10.2337/diab.30.11.960
Download citation file: