Possible role for calmodulin in insulin release. Studies with trifluoperazine in rat pancreatic islets

Abstract

The role of calmodulin in insulin secretion from rat pancreatic islets has been examined by the use of trifluoperazine, an inhibitor of calmodulin-Ca++ -directed functions. It was found that 30 μM trifluoperazine caused 50% inhibition, and 100 μM, up to 73% inhibition of 16.7 mM glucose-stimulated insulin release. 100 μM trifluoperazine caused a similar inhibition of 10 mM glyceraldehyde-stimulated release. Therefore, the site of action of trifluoperazine in glucose stimulus-secretion coupling apears to be after the trioses. As trifluoperazine had no effect upon insulin release stimulated by 1 mM 3-isobutyl-1-methylxanthine, the inhibitory effect of trifluoperazine appears to be rather specific. Further, the process of exocytosis per se is not affected. It was also found that although trifluoperazine inhibited the effect of glucose to stimulate insulin release, it did not affect the synergism between glucose and 3-isobutyl-1-methylxanthine to potentiate insulin release. It may be concluded that trifluoperazine selectively inhibits one part of the mechanism by which glucose stimulates insulin release. Calmodulin plays a role in the stimulation of insulin release by glucose at a site between metabolism of trioses and elevation of cytosol Ca++, but is not involved in the final process of exocytosis.